Aspergillus fumigatus Triggers Inflammatory Responses by Stage-Specific β-Glucan Display
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Inhalation of fungal spores (conidia) occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-alpha/MIP-2 secretion by alveolar macrophages. Fungal beta-glucans act as a trigger for the induction of these inflammatory responses through their time-dependent exposure on the surface of germinating conidia. Dectin-1, an innate immune receptor that recognizes fungal beta-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed beta-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-alpha/MIP-2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals provide an additive contribution to macrophage activation by germinating conidia. Selective responsiveness to germinating conidia provides the innate immune system with a mechanism to restrict inflammatory responses to metabolically active, potentially invasive fungal spores.
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Significant advances have been made in elucidating the main innate immune players and effector pathways for efficient control of Aspergillus infection in mouse models with the use of transgenic mice.
“Significant advances have been made in elucidating the main innate immune players and effector pathways for efficient control of Aspergillus infection in mouse models with the use of transgenic mice (189–202).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [194]
The discovery of selective activation of Dectin-1/Syk signaling during germination of Aspergillus conidia due to stage-specific surface exposure of β-glucan and the ability of PRR to regulate phagosome maturation provided the conceptual framework of PAMPs masking as a mechanism employed by fungi to escape macrophage killing.
“The discovery of selective activation of Dectin-1/Syk signaling during germination of Aspergillus conidia due to stage-specific surface exposure of β-glucan (194, 246, 247) and the ability of PRR to regulate phagosome maturation (248) provided the conceptual framework of pathogen-associated molecular patterns (PAMPs) masking as a mechanism employed by fungi to escape macrophage killing.”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [194]
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ResultImmune responses to human fungal pathogens and therapeutic prospects
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“Zymosan injection triggered severe chronic arthritis in genetically susceptible mice in a Dectin-1-dependent manner (34), and intratracheal administration of Aspergillus fumigatus conidia induced proinflammatory cytokine production, which was blocked by coadministration of either a soluble Dectin-1-Fc fusion protein o…”
BackgroundRandomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitization
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Hydrophobins—Unique Fungal Proteins
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“For example, Dectin-1 at the surface of the myeloid cells does not bind to conidia of A. fumigatus, whereas after conidial phagocytosis, the phagolysosome is strongly labelled with an anti-Dectin-1 antibody (Hohl et al., 2005).”
BackgroundBeyond pattern recognition: five immune checkpoints for scaling the microbial threat
Blander, J. M., & Sander, L. E. (2012) · Nature reviews. Immunology · doi:10.1038/nri3167 · Cited by 286 · see citing works
“Following germination, RodA is presumably degraded, exposing β-1,3-glucans (particularly at sites of hyphal extension), which signal a potentially threatening scenario and trigger the activation of PRRs such as dectin 1 (Ref”
Dynamic, Morphotype-Specific Candida albicans β-Glucan Exposure during Infection and Drug Treatment
Wheeler, R. T., Kombe, D., Agarwala, S. D., & Fink, G. R. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000227 · Cited by 309 · see citing works
Transcriptional programming of the dendritic cell network
Belz, G. T., & Nutt, S. L. (2012) · Nature reviews. Immunology · doi:10.1038/nri3149 · Cited by 282 · see citing works
“Under inflammatory conditions, circulating blood monocytes can be rapidly mobilized and can differentiate into cells that possess many prototypical features of DC”
BackgroundCurrent Perspectives on Echinocandin Class Drugs
Perlin, D. S. (2011) · Future Microbiology · doi:10.2217/fmb.11.19 · Cited by 274 · see citing works
“The innate immune system ignores the less threatening dormant conidia, but responds vigorously to germinating condia and hyphae [155].”
BackgroundKarki, R., Man, S. M., Malireddi, R. K. S., Gurung, P., Vogel, P., Lamkanfi, M., & Kanneganti, T.-D. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.01.006 · Cited by 272 · see citing works
“, 2008) and C-type lectin receptors (CLRs) dectin-1 (Hohl et al., 2005; Steele et al., 2005) and dectin-2 (Barrett et al.”
C-type lectin receptors in antifungal immunity
Willment, J. A., & Brown, G. D. (2007) · Trends in Microbiology · doi:10.1016/j.tim.2007.10.012 · Cited by 268 · see citing works
Immune defence to invasive fungal infections: A comprehensive review
Pathakumari, B., Liang, G., & Liu, W. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110550 · Cited by 272 · see citing works
Eduard, W. (2009) · Critical Reviews in Toxicology · doi:10.3109/10408440903307333 · Cited by 251 · see citing works
“…spores were applied� However, when spores were incubated until swollen before heat-killing, a similar inflammatory response was seen as induced by viable spores (Hohl et al�, 2005)� The applied dose (1 × 107 spores/animal, approximately 4 × 105 spores/g bw) was high compared to the doses used…”
BackgroundMethodInfluential<i>Aspergillus fumigatus</i> : Principles of Pathogenesis and Host Defense
Hohl, T. M., & Feldmesser, M. (2007) · Eukaryotic Cell · doi:10.1128/ec.00274-07 · Cited by 237 · see citing works
“observed for macrophages isolated from other sources (50, 78, 97).”
Self-citationInnate Immunity toAspergillusSpecies
Park, S. J., & Mehrad, B. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00014-09 · Cited by 230 · see citing works
“recognition by the host: the binding and ingestion of resting conidia, for example, induce very little inflammatory response (64, 74, 157), and optimal CD4 T-cell responses appear to occur only in response to live conidia (136).”
BackgroundWüthrich, M., Deepe, G. S., & Klein, B. S. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074958 · Cited by 225 · see citing works
“albicans) have developed mechanisms to mask their b-glucan exposure and limit detection by immune cells (Hohl et al. 2005; Steele et al. 2005; Wheeler et al. 2008).”
Advances in combating fungal diseases: vaccines on the threshold
Cutler, J. E., Deepe, G. S., & Klein, B. S. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1537 · Cited by 223 · see citing works
Aspergillus Cell Wall Melanin Blocks LC3-Associated Phagocytosis to Promote Pathogenicity
Akoumianaki, T., Kyrmizi, I., Valsecchi, I., Gresnigt, M. S., Samonis, G., Drakos, E., Boumpas, D., Muszkieta, L., Prevost, M.-C., Kontoyiannis, D. P., et al. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2015.12.002 · Cited by 218 · see citing works
“Surface exposure of these PAMPs upon biological (germination) or genetic removal of rodlet protein RodA (DrodA) (Aimanianda et al., 2009; Hohl et al., 2005; Steele et al., 2005) triggers potent immune cell activation.”
BackgroundMircescu, M. M., Lipuma, L., van Rooijen, N., Pamer, E. G., & Hohl, T. M. (2009) · The Journal of Infectious Diseases · doi:10.1086/600380 · Cited by 216 · see citing works
“A. fumigatus strain AF293 conidial suspensions were administered to anesthesized mice via the intratracheal route as described elsewhere [ 21 ].”
MethodSelf-citationNOX2-dependent regulation of inflammation
Singel, K. L., & Segal, B. H. (2016) · Clinical Science · doi:10.1042/cs20150660 · Cited by 214 · see citing works
Beyond autophagy: LC3-associated phagocytosis and endocytosis
Peña-Martinez, C., Rickman, A. D., & Heckmann, B. L. (2022) · Science Advances · doi:10.1126/sciadv.abn1702 · Cited by 212 · see citing works
Latgé, J.-P., Beauvais, A., & Chamilos, G. (2017) · Annual Review of Microbiology · doi:10.1146/annurev-micro-030117-020406 · Cited by 207 · see citing works
Tsoni, S. V., & Brown, G. D. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.019 · Cited by 207 · see citing works
Collaboration between the innate immune receptors dectin‐1, TLRs, and Nods
Underhill, D. M. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00548.x · Cited by 187 · see citing works
Carrion, S. D. J., Leal, S. M., Ghannoum, M. A., Aimanianda, V., Latgé, J., & Pearlman, E. M. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300748 · Cited by 187 · see citing works
“gatus (29, 30), less is known about the role of Dectin-2 during fungal infection.”
BackgroundZarember, K. A., Sugui, J. A., Chang, Y. C., Kwon-Chung, K. J., & Gallin, J. I. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.10.6367 · Cited by 184 · see citing works
Lamaris, G. A., Lewis, R. E., Chamilos, G., May, G. S., Safdar, A., Walsh, T. J., RAAD, I. I., & Kontoyiannis, D. P. (2008) · The Journal of Infectious Diseases · doi:10.1086/589305 · Cited by 186 · see citing works
LeibundGut‐Landmann, S., Wüthrich, M., & Hohl, T. M. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.04.007 · Cited by 186 · see citing works
Self-citationAspergillus Fumigatus : Cell Wall Polysaccharides, their Biosynthesis and Organization
Gastebois, A., Clavaud, C., Aimanianda, V., & Latgé, J. (2009) · Future Microbiology · doi:10.2217/fmb.09.29 · Cited by 181 · see citing works
Hyphal Growth in Human Fungal Pathogens and Its Role in Virulence
Brand, A. (2011) · International Journal of Microbiology · doi:10.1155/2012/517529 · Cited by 180 · see citing works
Aspergillus fumigatus: contours of an opportunistic human pathogen
McCormick, A., Loeffler, J., & Ebel, F. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01517.x · Cited by 181 · see citing works
“Interestingly, it is not traceable on hyphae (Hohl et al., 2005), a fact that has been discussed as a fungal stealth strategy.”
BackgroundDistinct Roles for Dectin-1 and TLR4 in the Pathogenesis of Aspergillus fumigatus Keratitis
Leal, S. M., Cowden, S., Hsia, Y. C., Ghannoum, M. A., Momany, M., & Pearlman, E. M. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000976 · Cited by 179 · see citing works
Herbst, S., Shah, A., Mazón, M. J., Marzola, V., Jensen, B., Reed, A. K., Birrell, M. A., Saijo, S., Mostowy, S., Shaunak, S., et al. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201404556 · Cited by 172 · see citing works
“…to AF appear more complexand involve both Dectin-1 and Dectin-2, as well as Toll-like receptors, complement and opsonins (Richardson et al, 1991; Madan et al, 1997; Hohl et al, 2005; Luther et al, 2007; Werner et al, 2009; Moalli et al, 2010; Hasenberg et al, 2011; Carrion Sdeet al, 2013).”
BackgroundSelective C-Rel Activation via Malt1 Controls Anti-Fungal TH-17 Immunity by Dectin-1 and Dectin-2
Gringhuis, S. I., Wevers, B. A., Kaptein, T. M., van Capel, T. M. M., Theelen, B., Boekhout, T., de Jong, E. C., & Geijtenbeek, T. B. H. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1001259 · Cited by 174 · see citing works
Recognition of fungal pathogens by Toll-like receptors
Netea, M., Graaf, C., Meer, J. T. M., & Kullberg, B. (2004) · European Journal of Clinical Microbiology and Infectious Diseases · doi:10.1007/s10096-004-1192-7 · Cited by 239 · see citing works
Immune responses to commensal and environmental microbes
Pamer, E. G. (2007) · Nature Immunology · doi:10.1038/ni1526 · Cited by 169 · see citing works
“fumigatus spores induce recruitment of inflammatory cells to the airways, and macrophages and dendritic cells distinguish between germinating and dormant spores in a TLR- and Dectin-1-dependent fashio”
Self-citationThywißen, A., Heinekamp, T., Dahse, H., Schmaler-Ripcke, J., Nietzsche, S., Zipfel, P. F., & Brakhage, A. A. (2011) · Frontiers in Microbiology · doi:10.3389/fmicb.2011.00096 · Cited by 161 · see citing works
“In recent years, the process by which conidia are recognized and ingested by professional phagocytes (Hohl et al., 2005; Luther et al., 2008; Bhatia et al., 2011) as well as non-professional phagocytes (Paris et al., 1997; Filler and Sheppard, 2006) has been studied extensively.”
The unexpected role of bioaerosols in the Oxidative Potential of PM
Samaké, A., Uzu, G., Martins, J., Calas, A., Vince, E., Parat, S., & Jaffrezo, J. ‐. (2017) · Scientific Reports · doi:10.1038/s41598-017-11178-0 · Cited by 158 · see citing works
Cushion, M. T., Linke, M. J., Ashbaugh, A., Sesterhenn, T., Collins, M. S., Lynch, K., Brubaker, R., & Walzer, P. D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008524 · Cited by 155 · see citing works
Rivera, A., Hohl, T. M., Collins, N., Leiner, I. M., Gallegos, A. M., Saijo, S., Coward, J., Iwakura, Y., & Pamer, E. G. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20100906 · Cited by 155 · see citing works
“Germinating A. fumigatus spores activate TLRs and Dectin-1 (Hohl et al., 2005; Rivera et al., 2005; Steele et al., 2005; Gersuk et al., 2006) and induce robust recruitment of inflammatory cells to JEM VOL. 208, February 14, 2011 Article 371 TCR-tg cells that were adoptively transferred into WT-B6 mice differentiated i…”
InfluentialSelf-citationDynamics of cell wall components of Magnaporthe grisea during infectious structure development
Fujikawa, T., Kuga, Y., Yano, S., Yoshimi, A., Tachiki, T., Abe, K., & Nishimura, M. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06786.x · Cited by 155 · see citing works
“…b-1,3-glucan-specific antibody (Biosupplies, Parkville, Australia) (0.1 mg ml-1 in PBS buffer) as the primary antibody and 20 ml Alexa Fluor 594 goat anti-mouse IgG (H + l) antibody (Invitrogen) (0.1 mg ml-1 in PBS buffer) as the secondary antibody (Hohl et al., 2005; Wheeler and Fink, 2006).”
MethodInfluentialFungal antioxidant pathways promote survival against neutrophils during infection
Leal, S. M., Vareechon, C., Cowden, S., Cobb, B. A., Latgé, J.-P., Momany, M., & Pearlman, E. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63239 · Cited by 146 · see citing works
“However, we have shown that dectin-1–/– mice exhibit defects in fungal killing in vivo (34, 56).”
BackgroundInteractions of Aspergillus fumigatus Conidia with Airway Epithelial Cells: A Critical Review
Croft, C. A., Culibrk, L., Moore, M. M., & Tebbutt, S. J. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00472 · Cited by 142 · see citing works
“Furthermore, inhibitors of actin polymerization and an anti-Dectin-1 antibody decreased both the amount of conidia internalized and the monolayer decay (Bertuzzi et al., 2014).”
BackgroundInfluentialKyrmizi, I., Gresnigt, M. S., Akoumianaki, T., Samonis, G., Sidiropoulos, P., Boumpas, D., Netea, M. G., van de Veerdonk, F. L., Kontoyiannis, D. P., & Chamilos, G. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300132 · Cited by 142 · see citing works
“fumigatus spores (28), we tested whether this could be the trigger for LC3 II recruitment in fungal phagosomes.”
BackgroundInfluentialAspergillus fumigatus Conidial Melanin Modulates Host Cytokine Response
Chai, L. Y. A., Netea, M. G., Sugui, J. A., Vonk, A. G., van de Sande, W. W. J., Warris, A., Kwon-Chung, K. J., & Kullberg, B. J. (2009) · Immunobiology · doi:10.1016/j.imbio.2009.10.002 · Cited by 141 · see citing works
“This has been corroborated recently by other groups, which had demonstrated a high concentration of accessible b-glucan on the conidial surface of a pksP deletant strain or on swollen conidia (Luther et al. 2007, Hohl et al. 2005).”
The Interaction of Human Pathogenic Fungi With C-Type Lectin Receptors
Goyal, S., Castrillón-Betancur, J. C., Klaile, E., & Slevogt, H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01261 · Cited by 142 · see citing works
“fumigatus conidia and germ tubes stimulated NF-κB activation, mediated the secretion of proinflammatory cytokines involved in the recruitment of neutrophils, and led to ROS production by human monocyte-derived macrophages, murine macrophages, and alveolar macrophages (AMs) (89, 92, 93).”
BackgroundRosas, M., Liddiard, K., Kimberg, M., Faro‐Trindade, I., McDonald, J. U., Williams, D. L., Brown, G. D., & Taylor, P. R. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.5.3549 · Cited by 139 · see citing works
Regulation of innate immunity by NADPH oxidase
Segal, B. H., Grimm, M. J., Khan, A. N. H., Han, W., & Blackwell, T. S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.04.022 · Cited by 139 · see citing works
Innate Immune Activation and CD4+ T Cell Priming during Respiratory Fungal Infection
Rivera, A., Ro, G. S., Epps, H. L. V., Simpson, T. R., Leiner, I. M., Sant’Angelo, D. B., & Pamer, E. G. (2006) · Immunity · doi:10.1016/j.immuni.2006.08.016 · Cited by 135 · see citing works
Self-citationHopke, A., Nicke, N., Hidu, E. E., Degani, G., Popolo, L., & Wheeler, R. T. (2016) · PLOS Pathogens · doi:10.1371/journal.ppat.1005644 · Cited by 131 · see citing works
Ben‐Ami, R., Lewis, R. E., & Kontoyiannis, D. P. (2010) · British Journal of Haematology · doi:10.1111/j.1365-2141.2010.08283.x · Cited by 132 · see citing works
“Recognition of BG by these innate cells triggers a robust inflammatory response that is independent of MyD88 signaling (Hohl et al, 2005).”
BackgroundChamilos, G., Ganguly, D., Lande, R., Gregorio, J. D., Meller, S., Goldman, W. E., Gilliet, M. F., & Kontoyiannis, D. P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012955 · Cited by 131 · see citing works
Fungal Chitin from Asthma-Associated Home Environments Induces Eosinophilic Lung Infiltration
Dyken, S. J. V., Garcia, D. A., Porter, P., Huang, X., Quinlan, P. J., Blanc, P. D., Corry, D. B., & Locksley, R. M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100972 · Cited by 131 · see citing works
“This innate response to insoluble hyphal fungal fragments, which, along with conidia, can become airborne and inhaled in the indoor environment (15), suggested a key role for exposed cell wall elements, consistent with prior studies demonstrating the requirement for conidial swelling or subsequent hyphal branching to…”
ResultImmune Interactions with Pathogenic and Commensal Fungi: A Two-Way Street
Underhill, D. M., & Pearlman, E. (2015) · Immunity · doi:10.1016/j.immuni.2015.10.023 · Cited by 130 · see citing works
“Dectin-1 is not activated by dormant Aspergillus conidia, which do not express b-glucan on the cell surface; however, after germination, b-glucan is exposed on the cell wall surface and can then be detected by Dectin-1 (Gersuk et al., 2006; Hohl et al., 2005; Steele et al., 2005).”
BackgroundThe innate immune response to Aspergillus fumigatus at the alveolar surface
Margalit, A., & Kavanagh, K. A. (2015) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuv018 · Cited by 129 · see citing works
“Elsewhere, it was reported that, Dectin-1 signaling pathways synergize with MyD88 signaling pathways to provide an optimum inflammatory response against swollen, but not resting A. fumigatus conidia (Hohl et al. 2005).”
BackgroundInfluentialChapter 5 Emergence of the Th17 Pathway and Its Role in Host Defense
O’Quinn, D. B., Palmer, M. T., Lee, Y. K., & Weaver, C. T. (2008) · Advances in immunology · doi:10.1016/s0065-2776(08)00605-6 · Cited by 126 · see citing works
Rapaka, R. R., Ricks, D. M., Alcorn, J. F., Chen, K., Khader, S. A., Zheng, M., Plevy, S. E., Bengtén, E., & Kolls, J. K. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20100034 · Cited by 125 · see citing works
“…of surface -1,3 glucan, were poorly reactive with natural IgM, whereas conidia matured to a swollen, prehyphal state, leading to cell wall remodeling, and the display of high quantities of surface -1,3 glucan (Hohl et al., 2005; Steele et al., 2005) bound significant quantities of IgM (Fig.”
BackgroundPathogenic Fungi Regulate Immunity by Inducing Neutrophilic Myeloid-Derived Suppressor Cells
Rieber, N. P., Singh, A., Öz, H. H., Carevic, M., Bouzani, M., Amich, J., Ost, M., Ye, Z., Ballbach, M., Schäfer, I., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.02.007 · Cited by 125 · see citing works
“The potency of A. fumigatus to induce MDSCs was most pronounced for germ tubes and hyphae, morphotypes charac- teristic for invasive fungal infections (Figure 1A) (Aimanianda et al., 2009; Hohl et al., 2005; Moyes et al., 2010).”
BackgroundKarthikeyan, R. S. G., Leal, S. M., Prajna, N. V., Dharmalingam, K., Geiser, D. M., Pearlman, E. M., & Lalitha, P. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir426 · Cited by 125 · see citing works
“Expression of b-Glucan and Characterization of the Cellular Infiltrate in Posttransplant Corneas Infected With Aspergillus or Fusarium Because Dectin-1 recognizes b-glucan on germinating conidia and hyphae [20], we next examined b-glucan expression in posttransplant infected corneas.”
BackgroundJhingran, A., Mar, K. B., Kumasaka, D. K., Knoblaugh, S. E., Ngo, L. Y., Segal, B. H., Iwakura, Y., Lowell, C. A., Hamerman, J. A., Lin, X., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.10.026 · Cited by 119 · see citing works
“and classified as described in Hohl et al. (2009). Tissue processing did not result in leukocyte uptake of exogenously added FLARE conidia.”
BackgroundMethodInfluentialSelf-citationRamirez-Ortiz, Z. G., Lee, C. K., Wang, J. P., Boon, L., Specht, C. A., & Levitz, S. M. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.04.007 · Cited by 121 · see citing works
“DGliZ, GliZ Comp, DLaeA, and LaeA Comp (Bok et al., 2005; Bok and Keller, 2004; Bouhired et al., 2007; Hohl et al., 2005) were generous gifts of Nancy Keller (University of Wisconsin, Madison, WI).”
BackgroundInterference of Aspergillus fumigatus with the immune response
Heinekamp, T., Schmidt, H., Lapp, K., Pähtz, V., Shopova, I., Köster-Eiserfunke, N., Krüger, T., Kniemeyer, O., & Brakhage, A. A. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-014-0465-1 · Cited by 123 · see citing works
“Swelling and germination of conidia are accompanied by a subsequent loss of the protective melanin and hydrophobin layer and thereby lead to an increasing exposure of immunological surface components and enhanced phagocytosis [16, 18].”
BackgroundHohl, T. M., Feldmesser, M., Perlin, D. S., & Pamer, E. G. (2008) · The Journal of Infectious Diseases · doi:10.1086/589304 · Cited by 119 · see citing works
“fumigatus strains Af293 and ATCC 90906 were cultured as described elsewhere [20].”
BackgroundMethodResultInfluentialSelf-citationBhatia, S., Fei, M., Yarlagadda, M., Qi, Z., Akira, S., Saijo, S., Iwakura, Y., van Rooijen, N., Gibson, G. A., Croix, C. M. S., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0015943 · Cited by 119 · see citing works
Adaptive Immunity to FungiPreprint
Verma, A. H., Wüthrich, M. D., Deepe, G. S., & Klein, B. S. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019612 · Cited by 119 · see citing works
“albicans) have developed mechanisms to mask their b-glucan exposure and limit detection by immune cells (Hohl et al. 2005; Steele et al. 2005; Wheeler et al. 2008).”
Chai, L. Y. A., de Boer, M. G. J., van der Velden, W. J. F. M., Plantinga, T. S., van Spriel, A. B., Jacobs, C. W. M., Halkes, C. J. M., Vonk, A. G., Blijlevens, N. M. A., van Dissel, J. T., et al. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiq102 · Cited by 118 · see citing works
“Results from in vitro and murine models have shown that Dectin-1 is pivotal in host defense against Aspergillus infection [8–10].”
BackgroundOlynych, T., Jakeman, D. L., & Marshall, J. S. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.06.008 · Cited by 116 · see citing works
Fungal pathogens—a sweet and sour treat for toll-like receptors
Bourgeois, C., & Kuchler, K. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00142 · Cited by 114 · see citing works
“Cell wall remodeling upon environmental stress or during hyphae formation may change PAMP composition and alter accessibility for TLRs as observed for many species (Hohl et al., 2005; Collette and Lorenz, 2011).”
BackgroundInvasive aspergillosis in glucocorticoid-treated patients
Lewis, R. E., & Kontoyiannis, D. P. (2008) · Medical Mycology · doi:10.1080/13693780802227159 · Cited by 114 · see citing works
Macrophages inhibit Aspergillus fumigatus germination and neutrophil-mediated fungal killing
Rosowski, E. E., Raffa, N., Knox, B. P., Golenberg, N., Keller, N. P., & Anna Huttenlocher, A. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007229 · Cited by 113 · see citing works
Leal, S. M., Roy, S., Vareechon, C., Carrion, S. D., Clark, H., Lopez-Berges, M. S., diPietro, A., Schrettl, M., Beckmann, N., Redl, B., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003436 · Cited by 111 · see citing works
“Expression of these iron-sequestering proteins was dependent on Dectin-1, which we and others showed is important in recognizing b-glucan on germinating conidia [23,35,36].”
BackgroundDubourdeau, M., Athman, R., Balloy, V., Huerre, M., Chignard, M., Philpott, D. J., Latgé, J., & Ibrahim-Granet, O. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.3994 · Cited by 111 · see citing works
“Our results and those of others (26, 27, 29) on the modulation of the expression of TNF- in macrophages after exposure to live but not heat-killed conidia for 6 h as well as to swollen conidia suggest that TNF- and IL-6 are essential cytokines in the host defense against exposure to A.”
BackgroundResultFungal glycans and the innate immune recognition
Barreto‐Bergter, E., & Figueiredo, R. T. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00145 · Cited by 110 · see citing works
“…of the inner layer of the fungal cell wall, as a result of the growth or germination, as observed during division and septation of C. albicans yeasts and hyphae, and germination of resting conidia of A. fumigatus (Gantner et al., 2005; Hohl et al., 2005; Steele et al., 2005; Gersuk et al., 2006).”
BackgroundSun, W., Lu, X., Li, X., Sun, Q.-Y., Su, X., Song, Y., Sun, H., & Shi, Y. P. (2012) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-012-1624-8 · Cited by 110 · see citing works
“fumigatus conidia were harvested and prepared as described in a previous study [16].”
MethodJhingran, A., Kasahara, S., Shepardson, K. M., Junecko, B. A. F., Heung, L. J., Kumasaka, D. K., Knoblaugh, S. E., Lin, X., Kazmierczak, B. I., Reinhart, T. A., et al. (2015) · PLOS Pathogens · doi:10.1371/journal.ppat.1004589 · Cited by 108 · see citing works
Self-citationSterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death
Shlezinger, N., Irmer, H., Dhingra, S., Beattie, S. R., Cramer, R. A., Braus, G. H., Sharon, A., & Hohl, T. M. (2017) · Science · doi:10.1126/science.aan0365 · Cited by 105 · see citing works
Self-citationFungal Recognition by TLR2 and Dectin-1
Goodridge, H. S., & Underhill, D. M. (2007) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-72167-3_5 · Cited by 105 · see citing works
“albicans however, β-glucan was also exposed on the surface of Aspergillus germ tubes and hyphae, which could therefore be detected by Dectin-1 (Hohl et al., 2005; Steele et al., 2005; Gersuk et al., 2006).”
BackgroundPulmonary aspergillosis: clinical presentation, diagnostic tests, management and complications
Sherif, R. D., & Segal, B. H. (2010) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0b013e328337d6de · Cited by 106 · see citing works
Murdock, B. J., Shreiner, A. B., McDonald, R. A., Osterholzer, J. J., White, E. S., Toews, G. B., & Huffnagle, G. B. (2010) · Infection and Immunity · doi:10.1128/iai.00508-10 · Cited by 105 · see citing works
“We did occasionally observe rare germinating conidia in some mice (data not shown), which is worth noting because germinating conidia are metabolically active and reorganize the contents of their cell walls to expose immunostimulatory glucans (32, 70).”
BackgroundBalloy, V., Sallenave, J.-M., Wu, Y., Touqui, L., Latgé, J.-P., Si-Tahar, M., & Chignard, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803149200 · Cited by 102 · see citing works
- Authors
- Hohl, T. M., Van Epps, H. L., Rivera, A., Morgan, L. A., Chen, P. L., Feldmesser, M., & Pamer, E. G.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Pamer, Eric G
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2005-11-18
- Volume
- 1
- Issue
- 3
- Pages
- e30
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC1287910
- OpenAlex
- W2041414113
- Cited by
- 428
- References
- 46
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 13 · 2023: 17 · 2022: 11 · 2021: 12 · 2020: 20 · 2019: 19 · 2018: 14 · 2017: 24 · 2016: 21 · 2015: 23 · 2014: 24 · 2013: 20 · 2012: 30
- FWCI
- 15.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Cape Town
- National Institutes of Health (NIH T32)
- U.S. Public Health Service
- National Institute of Allergy and Infectious Diseases (R03AI53623, R03AI053623)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Aspergillus fumigatus, β-glucan, conidial germination, Dectin-1, alveolar macrophages, TNF-α, CXCL2, neutrophil recruitment, innate immunity, TLR2, MyD88, fungal pathogenesis, invasive aspergillosis, phagosome
- MeSH terms
- Dectin-1, Animals, Aspergillosis, Aspergillus fumigatus, Dendritic Cells, Intubation, Intratracheal, Lung, Membrane Proteins, Mice, Inbred BALB C, Nerve Tissue Proteins, Pneumonia, Specific Pathogen-Free Organisms, Spores, Fungal, Cytokines, Macrophages, Alveolar, Mice, Knockout, Inhalation Exposure, Lectins, C-Type, beta-Glucans, Mice
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