The DOI matches its Crossref record; 56 of the 57 references it cites were found in a registry or an index.
Iron Overload Alters Innate and T Helper Cell Responses to Candida albicans in Mice
Abstract
The effect of iron overload on susceptibility of mice to Candida albicans infection and on the type of T helper (Th) immunity elicited was investigated. Iron overload greatly increased susceptibility to disseminated infection with low-virulence C. albicans cells of exogenous origin. The candidacidal activity and the ability to release nitric oxide and bioactive interleukin (IL)-12 were greatly impaired in neutrophils and macrophages from infected mice. CD4 T cells from spleens of iron-overloaded mice were found to produce high levels of IL-4 and IL-10 and low levels of interferon-gamma. Treatment of iron-overloaded mice with the iron chelator, deferoxamine, resulted in the cure of mice from infection, restored the antifungal effector and immunomodulatory functions of the phagocytic cells, and allowed the occurrence of CD4 Th1 protective antifungal responses. These data indicate that iron overload may negatively affect CD4 Th1 development in mice with candidiasis, a function efficiently restored by therapy with deferoxamine.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, accumulation of intracellular Fe in T cells mitigates the activation, differentiation, and proliferation of T H 1 cells while fostering T H type 2 (T H 2) responses, as illustrated in the context of Candida albicans infection in mice [69,71].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [69]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, immune control of Candida infection could be restored by the iron chelator deferoxamine (DFO) (Mencacci et al., 1997).”
From Iron in infection and immunity (2020) · cites this paper as Mencacci et al., 1997
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thus, macrophages loaded with iron lose their ability to clear infections with intracellular pathogens, such as Salmonella, Mycobacteria, Chlamydia, Candida, or Legionella (Mencacci et al., 1997; Chlosta et al., 2006; Nairz et al., 2007; Paradkar et al., 2008; Botella et al., 2012; Bellmann-Weiler et al., 2013) whereas reduction of iron levels or addition of iron chelators can improve infection”
From Iron at the interface of immunity and infection (2014) · cites this paper as Mencacci et al., 1997
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Iron overload in mice can hamper the protective Th1 response and ability to clear C. albicans infection (Mencacci et al., 1997; Ishida and Johansen, 2014).”
From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Mencacci et al., 1997
The cited source says what the claim attributes to it.
In the citing paper
“This pathway appears to be partly responsible for the beneficial clinical effects of iron chelators observed in several experimental infection systems (Mencacci et al., 1997; Fritsche et al., 2001; Ibrahim et al., 2007; Bellmann-Weiler et al., 2013; Nairz et al., 2013).”
From Iron at the interface of immunity and infection (2014) · cites this paper as Mencacci et al., 1997
In the citing paper
“Inhibition of TFR affects the proliferation of T cell subtypes differently with TH1 immune responses being more sensitive to intracellular iron depletion than TH2 (Thorson et al., 1991; Mencacci et al., 1997).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Mencacci et al., 1997
In the citing paper
“Specifically, the intracellular Fe content of Mø modulates their response to interferon c (IFNc) [68,69], a cytokine produced by activated natural killer (NK) cells and T helper type 1 (T H 1) cells, which plays a central role in driving Mø microbicidal activity [70].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [69]
In the citing paper
“This is in a line with observation that iron supplementation skews T-cell differentiation towards a Th-2 response [130,131] which is largely referred to a negative regulatory effect of iron on the activity of the central Th-1 cytokine interferon-gamma (IFN-γ) [132].”
From Iron in immune cell function and host defense (2021) · cites this paper as [130]
In the citing paper
“On one hand, macrophage iron overload is associated with the inhibition of IFN-γ-driven antimicrobial immune effector pathways such as nitric oxide synthase 2 (Nos2) expression, resulting in impaired control of intracellular microbes (Weiss et al., 1994; Mencacci et al., 1997; Oexle et al., 2003).”
From Genetic and Dietary Iron Overload Differentially Affect the Course of Salmonella Typhimurium Infection (2017) · cites this paper as Mencacci et al., 1997
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,515
Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., & Arnheim, N. (1985) · Science · doi:10.1126/science.2999980 · Cited by 8,956
The Instructive Role of Innate Immunity in the Acquired Immune Response
Fearon, D. T., & Locksley, R. M. (1996) · Science · doi:10.1126/science.272.5258.50 · Cited by 1,711
Weinberg, E. D. (1978) · Microbiological Reviews · doi:10.1128/mmbr.42.1.45-66.1978 · Cited by 1,254
Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., & Arnheim, N. (1992) · PubMed · Cited by 733
Iron regulates nitric oxide synthase activity by controlling nuclear transcription.
Weiss, G., Werner-Felmayer, G., Werner, E. R., Grünewald, K., Wachter, H., & Hentze, M. W. (1994) · The Journal of experimental medicine · doi:10.1084/jem.180.3.969 · Cited by 412
Boelaert, J. R., de Locht, M., Van Cutsem, J., Kerrels, V, Cantinieaux, B., Verdonck, A., Van Landuyt, H. W., & Schneider, Y. J. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116419 · Cited by 340
Self-citationRomani, L. R., Mencacci, A., Cenci, E., Spaccapelo, R., Toniatti, C., Puccetti, P., Bistoni, F., & Poli, V. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.4.1345 · Cited by 308
Self-citationIron metabolism in health and disease
Brock, J. H., Halliday, J. W., Pippard, M. J., & Powell, L. W. (1994) · Cited by 286
Candidiasis in cancer patients.
Zai, S., Khan, S., & Gillani, J. A. (1997) · PubMed · Cited by 251
Cenci, E., Romani, L. R., Mencacci, A., Spaccapelo, R., Schiaffella, E., Puccetti, P., & Bistoni, F. (1993) · European Journal of Immunology · doi:10.1002/eji.1830230508 · Cited by 244
Self-citationLinkage of cell-mediated immunity to iron metabolism
Weiss, G., Wachter, H., & Fuchs, D. (1995) · Immunology Today · doi:10.1016/0167-5699(95)80034-4 · Cited by 200
An immunoregulatory role for neutrophils in CD4+ T helper subset selection in mice with candidiasis
Romani, L., Mencacci, A., Cenci, E., Del Sero, G., Bistoni, F., & Puccetti, P. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.5.2356 · Cited by 191
Self-citationRomani, L. R., Mencacci, A., Grohmann, U., Mocci, S., Mosci, P., Puccetti, P., & Bistoni, F. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.1.19 · Cited by 187
Self-citationRomani, L. R., Mocci, S., Bietta, C., Lanfaloni, L., Puccetti, P., & Bistoni, F. (1991) · Infection and Immunity · doi:10.1128/iai.59.12.4647-4654.1991 · Cited by 186
Self-citationRomani, L. R., Puccetti, P., Mencacci, A., Cenci, E., Spaccapelo, R., Tonnetti, L., Grohmann, U., & Bistoni, F. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.7.3514 · Cited by 182
Self-citationRomani, L. R., Mencacci, A., Cenci, E., et al. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.3.925 · Cited by 162
Self-citationBoelaert, J. R., Weinberg, G. A., & Ed, W. (1996) · PubMed · Cited by 157
Self-citationCHRONIC MUCO-CUTANEOUS CANDIDIASIS: ASSOCIATED ABNORMALITIES OF IRON METABOLISM
Higgs, J. M., & Wells, R. S. (1972) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1972.tb15420.x · Cited by 149
Romani, L. R., Mencacci, A., Tonnetti, L., Spaccapelo, R., Cenci, E., Puccetti, P., Wolf, S., & Bistoni, F. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.11.5167 · Cited by 133
Self-citationCenci, E., Mencacci, A., Spaccapelo, R., Tonnetti, L., Mosci, P., Enssle, K.-H., Puccetti, P., Romani, L. R., & Bistoni, F. (1995) · The Journal of Infectious Diseases · doi:10.1093/infdis/171.5.1279 · Cited by 130
Self-citationA TH1-TH2-like switch in candidiasis: new perspectives for therapy
Puccetti, P., Romani, L. R., & Bistoni, F. (1995) · Trends in Microbiology · doi:10.1016/s0966-842x(00)88931-3 · Cited by 128
Self-citationFunctional defects in phagocytic cells from patients with iron overload
van Asbeck, B. S., Marx, J. J. M., Struyvenberg, A., & Verhoef, J. (1984) · Journal of Infection · doi:10.1016/s0163-4453(84)93955-0 · Cited by 110
Effects of deferoxamine, feroxamine and iron on experimental mucormycosis (zygomycosis)
Cutsem, J. V., & Boelaert, J. R. (1989) · Kidney International · doi:10.1038/ki.1989.301 · Cited by 105
Self-citationListeria monocytogenes meningitis and decreased phagocytosis associated with iron overload.
van Asbeck, B. S., Verbrugh, H. A., van Oost, B. A., Marx, J. J. M., Imhof, H. W., & Verhoef, J. (1982) · BMJ · doi:10.1136/bmj.284.6315.542 · Cited by 104
Waterlot, Y., Cantinieaux, B., Hariga-Muller, C., De Maertelaere-Laurent, E., Vanherweghem, J., & Fondu, P. (1985) · BMJ · doi:10.1136/bmj.291.6494.501 · Cited by 100
Biological Role of Th Cell Subsets in Candidiasis
Romano, L., Puccetti, P., & Bistoni, F. (1996) · Chemical immunology/Fortschritte der Allergielehre/Progress in allergy/Chemical immunology and allergy · doi:10.1159/000319496 · Cited by 99
Self-citationImmune cell functions in iron overload.
de Sousa, M. A. B. (1989) · PubMed Central · Cited by 98
Reversal of Serum Fungistasis by Addition of Iron
Caroline, L., Taschdjian, C. L., Kozinn, P. J., & Schade, A. L. (1964) · Journal of Investigative Dermatology · doi:10.1038/jid.1964.90 · Cited by 98
Thorson, J. A., Smith, K. M., Gomez, F., Naumann, P. W., & Kemp, J. D. (1991) · Cellular Immunology · doi:10.1016/0008-8749(91)90336-a · Cited by 98
Elevated Serum Iron, Low Unbound Transferrin and Candidiasis in Acute Leukemia
Caroline, L., Rosner, F., & Kozinn, P. J. (1969) · Blood · doi:10.1182/blood.v34.4.441.441 · Cited by 97
Cure of Murine Candidiasis by Recombinant Soluble Interleukin-4 Receptor
Puccetti, P., Mencacci, A., Cenci, E., Spaccapelo, R., Mosci, P., Enssle, K.-H., Romani, L. R., & Bistoni, F. (1994) · The Journal of Infectious Diseases · doi:10.1093/infdis/169.6.1325 · Cited by 92
Self-citationSpaccapelo, R., Romani, L. R., Tonnetti, L., Cenci, E., Mencacci, A., Sero, G. D., Tognellini, R., Reed, S. G., Puccetti, P., & Bistoni, F. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.3.1349 · Cited by 91
Self-citationA role for complement receptor-like molecules in iron acquisition by Candida albicans
Moors, M. A., Stull, T. L., Blank, K. J., Buckley, H. R., & Mosser, D. M. (1992) · The Journal of experimental medicine · doi:10.1084/jem.175.6.1643 · Cited by 80
Weinberg, E. D., & Weinberg, G. A. (1995) · Current Opinion in Infectious Diseases · doi:10.1097/00001432-199506000-00004 · Cited by 80
Romani, L. R., Mencacci, A., Tonnetti, L., Spaccapelo, R., Cenci, E., Wolf, S. F., Puccetti, P., & Bistoni, F. (1994) · European Journal of Immunology · doi:10.1002/eji.1830240419 · Cited by 78
Self-citationMechanisms of resistance to fungal infections
Romani, L. R. (1995) · Current Opinion in Immunology · doi:10.1016/0952-7915(95)80097-2 · Cited by 77
Self-citationEsterly, N. B., Brammer, S. R., & Crounse, R. G. (1967) · Journal of Investigative Dermatology · doi:10.1038/jid.1967.162 · Cited by 73
CD4+ T-helper-cell responses in mice with low-level Candida albicans infection
Mencacci, A., Spaccapelo, R., Sero, G. D., Enssle, K.-H., Cassone, A., Bistoni, F., & Romani, L. R. (1996) · Infection and Immunity · doi:10.1128/iai.64.12.4907-4914.1996 · Cited by 71
Self-citationBistoni, F., Cenci, E., Mencacci, A., Schiaffella, E., Mosci, P., Puccetti, P., & Romani, L. R. (1993) · The Journal of Infectious Diseases · doi:10.1093/infdis/168.6.1449 · Cited by 70
Self-citationInhibition of Growth of Pathogenic Yeasts by Human Serum*
Roth, F. J., & Goldstein, M. I. (1961) · Journal of Investigative Dermatology · doi:10.1038/jid.1961.59 · Cited by 66
Gamma interferon modifies CD4+ subset expression in murine candidiasis
Romani, L. R., Cenci, E., Mencacci, A., Spaccapelo, R., Grohmann, U., Puccetti, P., & Bistoni, F. (1992) · Infection and Immunity · doi:10.1128/iai.60.11.4950-4952.1992 · Cited by 66
Self-citationSiderophore production by the pathogenic yeast, Candida albicans
Ismail, A., Bedell, G. W., & Lupan, D. M. (1985) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(85)90499-1 · Cited by 63
Iron metabolism and fungal infections in patients with haematological malignancies
Iglesias-Osma, C., Gonzalez-Villaron, L., San Miguel, J. F., Caballero, M. D., Vazquez, L., & de Castro, S. (1995) · Journal of Clinical Pathology · doi:10.1136/jcp.48.3.223 · Cited by 60
Interleukin-12 Gene-Expression of Macrophages Is Regulated by Nitric Oxide
Rothe, H., Hartmann, B., Geerlings, P., & Kolb, H. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1000 · Cited by 57
Deferoxamine enhances phagocytic function of human polymorphonuclear leukocytes
van Asbeck, B. S., Marx, J. J. M., Struyvenberg, A., van Kats-Renaud, J. H., & Verhoef, J. (1984) · Blood · doi:10.1182/blood.v63.3.714.714 · Cited by 50
IL12 in Candida albicans infections
Romani, L. R., Bistoni, F., Mencacci, A., Cenci, E., Spaccapelo, R., & Puccetti, P. (1995) · Research in Immunology · doi:10.1016/0923-2494(96)83028-8 · Cited by 42
Self-citationAntifungal activity of transferrin
Shiraishi, A., & Arai, T. (1979) · Medical Mycology · doi:10.1080/00362177985380101 · Cited by 39
Karp, J. E., & Merz, W. G. (1986) · Journal of Clinical Oncology · doi:10.1200/jco.1986.4.2.216 · Cited by 35 · cited 2×
“In this regard, it has been reported that the high risk of disseminated fungal infections observed in leukemic patients is attributable to increased serum iron and decreased iron-binding capacity [39-41].”
BackgroundAutenrieth, I. B., Bohn, E., Ewald, J. H., & Heesemann, J. (1995) · The Journal of Infectious Diseases · doi:10.1093/infdis/172.2.490 · Cited by 33
Desferrioxamine improves neutrophil phagocytosis in thalassemia major
Cantinieaux, B., Hariga-Muller, C., Fondu, P., Ferster, A., & Toppet, M. (1990) · American Journal of Hematology · doi:10.1002/ajh.2830350104 · Cited by 31
Opportunistic infections in the acquired immune deficiency syndrome.
Armstrong, D. (1987) · PubMed · Cited by 28
Experimental candidiasis in iron overload
Abe, F., Tateyma, M., Shibuya, H., Azumi, N., & Ommura, Y. (1985) · Mycopathologia · doi:10.1007/bf00437134 · Cited by 27
Effect of pH and Iron Concentration on Growth of Candida albicans in Human Serum
Elin, R. J., & Wolff, S. M. (1973) · The Journal of Infectious Diseases · doi:10.1093/infdis/127.6.705 · Cited by 27
Apasov, S. G., & Sitkovsky, M. V. (2006) · Birkhäuser-Verlag eBooks · doi:10.1007/3-7643-7408-x_2 · Cited by 23
Scholz, M., Blaheta, R. A., Henrich, D. M., Činátl, J., Markus, B. H., Doerr, H. W., & Cinatl, J. J. (1996) · Transplantation · doi:10.1097/00007890-199611150-00037 · Cited by 13
Research works printed but not linked: 1
- Romani L, Mencacci A, Cenci E, et al. Impaired neutrophil response and CD4 / Th1 development in IL-6 -deficient mice infected with Candida Whatever the mechanisms through which iron regulates Th albicans. J Exp Med 1996; 183:1345 -55.
Cited by
Sorted by citations
Neutrophil-Derived Proteins: Selling Cytokines by the Pound
Cassatella, M. A. (1999) · Advances in immunology · doi:10.1016/s0065-2776(08)60791-9 · Cited by 558
Iron, anaemia, and inflammatory bowel diseases
Gasché, C., Lomer, M. C. E., Cavill, I., & Weiss, G. (2004) · Gut · doi:10.1136/gut.2003.035758 · Cited by 501
KDIGO clinical practice guidelines for bisphosphonate treatment in chronic kidney disease
Woo, K. T., & Chan, C. M. (2011) · Kidney International · doi:10.1038/ki.2011.202 · Cited by 412
Koskenkorva-Frank, T. S., Weiss, G., Koppenol, W. H., & Burckhardt, S. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.09.001 · Cited by 406
The struggle for iron - a metal at the host-pathogen interface: Iron at the host-pathogen interface
Nairz, M., Schroll, A., Sonnweber, T., & Weiss, G. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01529.x · Cited by 398
“On the other hand, iron overload inhibits IFN-g activity and shifts the Th1/Th2 differentiation towards a Th2 type reaction characterized by increased production of IL-4 and IL-10 (Mencacci et al., 1997).”
Background
Metadata
- Authors
- Mencacci, A., Cenci, E., Boelaert, J. R., Bucci, P., Mosci, P., d'Ostiani, C. F., Bistoni, F., & Romani, L.
- Affiliations
- University of Perugia (IT)
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-06
- Volume
- 175
- Issue
- 6
- Pages
- 1467-1476
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2150374661
- Semantic Scholar
- 599845e36faeaa77f8bb9150b69754059dcae780
- Cited by
- 169
- References
- 57
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 10 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 4 · 2013: 9 · 2012: 8
- FWCI
- 6.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- iron overload, Candida albicans, candidiasis, deferoxamine, iron chelation, Th1 cells, CD4+ T cells, neutrophils, macrophages, nitric oxide, IL-12, IL-4, IL-10, interferon-gamma, antifungal immunity, disseminated fungal infection, immunomodulation
- MeSH terms
- Animals, Candida albicans, Candidiasis, Deferoxamine, Disease Susceptibility, Ferric Compounds, Immunoglobulin E, Iron, Iron Chelating Agents, Kidney, Liver, Macrophages, Mice, Inbred BALB C, Neutrophils, Nitrates, Nitric Oxide, RNA, Gene Expression, Cytokines, Th1 Cells, Nitric Oxide Synthase, Iron Overload, Mice
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
