Foamy Macrophages from Tuberculous Patients' Granulomas Constitute a Nutrient-Rich Reservoir for M. tuberculosis Persistence
Open accessAbstract
Tuberculosis (TB) is characterized by a tight interplay between Mycobacterium tuberculosis and host cells within granulomas. These cellular aggregates restrict bacterial spreading, but do not kill all the bacilli, which can persist for years. In-depth investigation of M. tuberculosis interactions with granuloma-specific cell populations are needed to gain insight into mycobacterial persistence, and to better understand the physiopathology of the disease. We have analyzed the formation of foamy macrophages (FMs), a granuloma-specific cell population characterized by its high lipid content, and studied their interaction with the tubercle bacillus. Within our in vitro human granuloma model, M. tuberculosis long chain fatty acids, namely oxygenated mycolic acids (MA), triggered the differentiation of human monocyte-derived macrophages into FMs. In these cells, mycobacteria no longer replicated and switched to a dormant non-replicative state. Electron microscopy observation of M. tuberculosis-infected FMs showed that the mycobacteria-containing phagosomes migrate towards host cell lipid bodies (LB), a process which culminates with the engulfment of the bacillus into the lipid droplets and with the accumulation of lipids within the microbe. Altogether, our results suggest that oxygenated mycolic acids from M. tuberculosis play a crucial role in the differentiation of macrophages into FMs. These cells might constitute a reservoir used by the tubercle bacillus for long-term persistence within its human host, and could provide a relevant model for the screening of new antimicrobials against non-replicating persistent mycobacteria.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Both mycobacterial phagosomes and chlamydiophorous vacuoles interact with lipid bodies during bacterial dormancy.
“Both mycobacterial phagosomes and chlamydiophorous vacuoles interact with lipid bodies during bacterial dormancy (50, 51).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [50]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Brennan, P. J., & Nikaido, H. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.000333 · Cited by 1,953 · see citing works
Mycobacterial persistence requires the utilization of host cholesterol
Pandey, A. K., & Sassetti, C. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711159105 · Cited by 1,064 · see citing works
Global Tuberculosis Control 2011, WHO Report 2011
Behera, D. (2012) · The Indian Journal of Medical Research · Cited by 1,022 · see citing works
Inhibition of Respiration by Nitric Oxide Induces a Mycobacterium tuberculosis Dormancy Program
Voskuil, M. I., Schnappinger, D., Visconti, K. C., Harrell, M. I., Dolganov, G., Sherman, D. R., & Schoolnik, G. K. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030205 · Cited by 971 · see citing works
The biogenesis and functions of lipid bodies in animals, plants and microorganisms
Murphy, D. J. (2001) · Progress in Lipid Research · doi:10.1016/s0163-7827(01)00013-3 · Cited by 966 · see citing works
The Surface of Lipid Droplets Is a Phospholipid Monolayer with a Unique Fatty Acid Composition
Tauchi-Sato, K., Ozeki, S., Houjou, T., Taguchi, R., & Fujimoto, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207712200 · Cited by 753 · see citing works
The Envelope Layers of Mycobacteria with Reference to their Pathogenicity
Daffé, M., & Draper, P. (1997) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/s0065-2911(08)60016-8 · Cited by 727 · see citing works
Self-citationRegulation of the Mycobacterium tuberculosis hypoxic response gene encoding α-crystallin
Sherman, D. R., Voskuil, M. I., Schnappinger, D., Liao, R., Harrell, M. I., & Schoolnik, G. K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121172498 · Cited by 725 · see citing works
Diagnostic Standards and Classification of Tuberculosis
Friedman, L. N. (1991) · American Review of Respiratory Disease · doi:10.1164/ajrccm/143.4_pt_1.895a · Cited by 431 · see citing works
Latent tuberculosis: mechanisms of host and bacillus that contribute to persistent infection
Tufariello, J. M., Chan, J., & Flynn, J. L. (2003) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(03)00741-2 · Cited by 401 · see citing works
Diagnostic Standards and Classification of Tuberculosis
(1990) · American Review of Respiratory Disease · doi:10.1164/ajrccm/142.3.725 · Cited by 401 · see citing works
Daniel, J., Deb, C., Dubey, V., Sirakova, T., Abomoelak, B., Morbidoni, H. R., & Kolattukudy, P. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.15.5017-5030.2004 · Cited by 364 · see citing works
Microbial Pathogenesis of Mycobacterium tuberculosis: Dawn of a Discipline
Glickman, M. S., & Jacobs, W. R. (2001) · Cell · doi:10.1016/s0092-8674(01)00236-7 · Cited by 352 · see citing works
STUDIES ON THE VIRULENCE OF TUBERCLE BACILLI
Bloch, H. (1950) · The Journal of Experimental Medicine · doi:10.1084/jem.91.2.197 · Cited by 339 · see citing works
Oxygenated mycolic acids are necessary for virulence of <i>Mycobacterium tuberculosis</i> in mice
Dubnau, E., Chan, J., Raynaud, C., Mohan, V. P., Lanéelle, M., Yu, K., Quémard, A., Smith, I., & Daffé, M. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.01882.x · Cited by 335 · see citing works
Self-citationIs Adipose Tissue a Place for Mycobacterium tuberculosis Persistence?
Neyrolles, O., Hernández-Pando, R., Piétri-Rouxel, F., Fornés, P., Tailleux, L., Payán, J., Pivert, E., Bordat, Y., Aguilar, D., Prévost, M., et al. (2006) · PLoS ONE · doi:10.1371/journal.pone.0000043 · Cited by 318 · see citing works
Restraining mycobacteria: Role of granulomas in mycobacterial infections
Saunders, B. M., & Cooper, A. M. (2000) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.2000.00933.x · Cited by 303 · see citing works
D’Avila, H., Melo, R. C. N., Parreira, G. G., Werneck-Barroso, E., Castro-Faria-Neto, H. C., & Bozza, P. T. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.5.3087 · Cited by 289 · see citing works
Deb, C., Daniel, J., Sirakova, T. D., Abomoelak, B., Dubey, V. S., & Kolattukudy, P. E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505556200 · Cited by 276 · see citing works
Global Tuberculosis Control: WHO Report 2011
Williams, C. (2012) · Australian and New Zealand Journal of Public Health · doi:10.1111/j.1753-6405.2012.00928.x · Cited by 268 · see citing works
Rao, V., Fujiwara, N., Porcelli, S. A., & Glickman, M. S. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041668 · Cited by 238 · see citing works
Intracellular lipophilic inclusions of mycobacteria in vitro and in sputum
Garton, N. J., Christensen, H., Minnikin, D. E., Adegbola, R. A., & Barer, M. R. (2002) · Microbiology · doi:10.1099/00221287-148-10-2951 · Cited by 225 · see citing works
Peyron, P., Bordier, C., N′Diaye, E.-N., & Maridonneau-Parini, I. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.9.5186 · Cited by 202 · see citing works
Self-citationGeisel, R. E., Sakamoto, K., Russell, D. G., & Rhoades, E. R. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.5007 · Cited by 190 · see citing works
Kalayoglu, M. V., & Byrne, G. I. (1998) · Infection and Immunity · doi:10.1128/iai.66.11.5067-5072.1998 · Cited by 188 · see citing works
Pathology of postprimary tuberculosis in humans and mice: Contradiction of long-held beliefs
Hunter, R. L., Jagannath, C., & Actor, J. K. (2007) · Tuberculosis · doi:10.1016/j.tube.2006.11.003 · Cited by 180 · see citing works
Yuan, Y., Zhu, Y., Crane, D. D., et al. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.01026.x · Cited by 176 · see citing works
Puisségur, M.-P., Botanch, C., Duteyrat, J.-L., Delsol, G., Caratero, C., & Altare, F. (2004) · Cellular Microbiology · doi:10.1111/j.1462-5822.2004.00371.x · Cited by 169 · see citing works
Self-citationMycobacterium tuberculosiscell envelope lipids and the host immune response
Karakousis, P. C., Bishai, W. R., & Dorman, S. E. (2004) · Cellular Microbiology · doi:10.1046/j.1462-5822.2003.00351.x · Cited by 152 · see citing works
Korf, H., Stoltz, A. C., Verschoor, J. A., BAETSELIER, P. D., & Grooten, J. (2005) · European Journal of Immunology · doi:10.1002/eji.200425332 · Cited by 133 · see citing works
de Chastellier, C., & Thilo, L. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2005.00617.x · Cited by 118 · see citing works
Self-citationLay, G., Poquet, Y., Salek-Peyron, P., et al. (2006) · The Journal of Pathology · doi:10.1002/path.2092 · Cited by 114 · see citing works
Self-citationCaveolin, Cholesterol, and Lipid Droplets?
Gerrit van, M. E. E. R. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.5.f29 · Cited by 113 · see citing works
Evolution of Granulomas in Lungs of Mice Infected Aerogenically with Mycobacterium tuberculosis
Cardona, P.-J. (2000) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2000.00763.x · Cited by 110 · see citing works
Self-citationPuisségur, M.-P., Lay, G., Gilleron, M., Botella, L., Nigou, J., Marrakchi, H., Mari, B. P., Duteyrat, J.-L., Guérardel, Y., Kremer, L., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.5.3161 · Cited by 110 · see citing works
Self-citationPathogenesis of Human Pulmonary Tuberculosis
Dannenberg, A. M. (2006) · ASM Press eBooks · doi:10.1128/9781555815684 · Cited by 108 · see citing works
Cardona, P.-J., Gordillo, S., Dı́az, J., et al. (2003) · Infection and Immunity · doi:10.1128/iai.71.10.5845-5854.2003 · Cited by 102 · see citing works
Self-citationFurther Insight into S-Adenosylmethionine-dependent Methyltransferases
Boissier, F., Bardou, F., Guillet, V., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510250200 · Cited by 72 · see citing works
Self-citationButon, X., Mamdouh, Z., Ghosh, R. N., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32112 · Cited by 68 · see citing works
Rationale for the histological spectrum of tuberculosis. A basis for classification
Ridley, D. S., & Ridley, M. J. (1987) · Pathology · doi:10.3109/00313028709077132 · Cited by 59 · see citing works
[Taxonomic value of mycobacterial fatty acids: proposal for a method of analysis].
Daffé, M., Lanéelle, M. A., Asselineau, C., et al. (1984) · PubMed · Cited by 53 · see citing works
Self-citationMüller, H., & Krüger, S. (1994) · Immunobiology · doi:10.1016/s0171-2985(11)80441-9 · Cited by 51 · see citing works
Fréhel, C., Offredo, C., & de Chastellier, C. (1997) · Infection and Immunity · doi:10.1128/iai.65.7.2792-2802.1997 · Cited by 36 · see citing works
Identification ofMycobacterium aviumgenes up-regulated in cultured macrophages and in mice
Danelishvili, L., Poort, M. J., & Bermudez, L. E. (2004) · FEMS Microbiology Letters · doi:10.1016/j.femsle.2004.08.014 · Cited by 35 · see citing works
Pagel, W., & Pagel, M. (1925) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf01891650 · Cited by 30 · see citing works
Studies on the virulence of Tubercle bacilli; the effect of cord factor on murine tuberculosis.
Blöch, H., & Noll, H. (1955) · PubMed · Cited by 27 · see citing works
:Pathogenesis of Human Pulmonary Tuberculosis: Insights from the Rabbit Model
Dannenberg, A. M., & Cook, J. L. (2007) · Clinical Infectious Diseases · doi:10.1086/513586 · Cited by 25 · see citing works
Localization and retention of mycobacterial antigen in lymph nodes of leprosy patients.
Barros, U., Ladiwala, U., Birdi, T. J., et al. (1987) · PubMed · Cited by 8 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [28]Florey H Oxford Uo, editor 1958 Tuberculosis. General pathology based on lectures delivered at the sir william dunn school of pathology Philadelphia and London W.B. Saunders 829 870
- [47]Goren M Brennan P 1979 Mycobacterial lipids: chemistry and biological activities. Youmans GP Tuberculosis Philadelphia WB Saunders
Cited by
Sorted by citations
Macrophage defense mechanisms against intracellular bacteria
Weiss, G., & Schaible, U. E. (2015) · Immunological Reviews · doi:10.1111/imr.12266 · Cited by 989 · see citing works
Intracellular Mycobacterium tuberculosis Exploits Host-derived Fatty Acids to Limit Metabolic Stress
Lee, W., VanderVen, B. C., Fahey, R. J., & Russell, D. G. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.445056 · Cited by 424 · see citing works
Singh, V., Jamwal, S., Jain, R., Verma, P., Gokhale, R., & Rao, K. V. S. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.09.012 · Cited by 295 · see citing works
Stanley, S. A., Barczak, A. K., Silvis, M. R., Luo, S. S., Sogi, K., Vokes, M., Bray, M.-A., Carpenter, A. E., Moore, C. B., Siddiqi, N., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1003946 · Cited by 251 · see citing works
Pernas, L., Bean, C., Boothroyd, J. C., & Scorrano, L. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.018 · Cited by 144 · see citing works
Melo, R. C. N., & Dvorak, A. M. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002729 · Cited by 139 · see citing works
Cutting Edge: Vitamin D Regulates Lipid Metabolism in <i>Mycobacterium tuberculosis</i> Infection
Salamon, H., Bruiners, N., Lakehal, K., Shi, L., Ravi, J., Yamaguchi, K. D., Pine, R., & Gennaro, M. L. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400736 · Cited by 99 · see citing works
Puckett, S., Trujillo, C., Eoh, H., Marrero, J., Spencer, J., Jackson, M., Schnappinger, D., Rhee, K., & Ehrt, S. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004144 · Cited by 72 · see citing works
- Authors
- Peyron, P., Vaubourgeix, J., Poquet, Y., Levillain, F., Botanch, C., Bardou, F., Daffé, M., Emile, J.-F., Marchou, B., Cardona, P.-J., de Chastellier, C., & Altare, F.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Hôpital Ambroise-Paré (FR)
- Hôpital Purpan (FR)
- Corresponding author
- Altare, Frédéric
- ORCID
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-11-11
- Volume
- 4
- Issue
- 11
- Pages
- e1000204
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2575403
- OpenAlex
- W2091442643
- Cited by
- 751
- References
- 48
- Citations by year
- 2026: 40 · 2025: 42 · 2024: 42 · 2023: 41 · 2022: 47 · 2021: 46 · 2020: 48 · 2019: 55 · 2018: 52 · 2017: 48 · 2016: 46 · 2015: 36 · 2014: 43 · 2013: 42 · 2012: 52
- FWCI
- 15.00
- 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)
- Figshare (submittedVersion, cc-by)
- Funders
- Styrelsen för Internationellt Utvecklingssamarbete
- Agence Nationale de la Recherche
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- foam cells, Mycobacterium tuberculosis, granuloma, bacterial persistence, long-chain fatty acids, lipid droplets, phagosome, monocyte-derived macrophages
- MeSH terms
- Cell Differentiation, Foam Cells, Granuloma, Humans, Lipids, Macrophages, Mycobacterium Infections, Mycobacterium tuberculosis, Mycolic Acids, Phagocytosis, Tuberculosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
