How Histoplasma Evades the Human Immune System

Authors

  • Albert Jefferson Kurniawan School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
  • Jolene Eleora Mok School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
  • Anathapindika Putra School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesiaq
  • Sem Samuel Surja Department of Parasitology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia

DOI:

https://doi.org/10.5644/ama2006-124.494

Keywords:

Histoplasmosis, Immune Evasion, Pathogenesis, Host-Pathogen Interaction

Abstract

This review summarises the current knowledge of the interactions between Histoplasma capsulatum (Hc) and the human immune system, with particular emphasis on host immune responses and fungal immune evasion mechanisms that modulate disease pathogenesis and clinical outcomes. Histoplasmosis is a disease caused by Hc, a fungus found worldwide. Upon inhala- tion, complex interactions occur between the pathogen and the human immune system, primarily involving the recognition of fungal cell wall components. Both innate and adaptive immune responses are orchestrated to eliminate the fungus through a tightly regulated balance. However, Hc has evolved multiple strategies to evade host defences and establish infection. The clinical spectrum of histoplasmosis varies, ranging from isolated pulmonary involvement to disseminated disease, depending on host factors and pathogen characteristics.

Conclusion. Overall, host-pathogen interactions between Hc and the human immune system play a central role in determining disease outcomes and represent key targets for improving preventive, diagnostic, and treatment strategies. 

References

Bongomin F, Kwizera R, Denning DW. Getting Histoplasmosis on the Map of International Recommendations for Patients with Advanced HIV Disease. J Fungi. 2019;5(3):80. doi: 10.3390/jof5030080.

Mittal J, Ponce MG, Gendlina I, Nosanchuk JD. Histoplasma Capsulatum: Mechanisms for Pathogenesis. Curr Top Microbiol Immunol. 2019;422:157-91. doi: 10.1007/82_2018_114.

Efrim ND, Dumea E, Cernat RC, Efrim ND, Dumea E, Cernat RC. Epidemiology of Histoplasmosis. In: Histo- plasmosis - A Comprehensive Study of Epidemiology, Pathogenesis, Diagnosis, and Treatment [Internet]. In- techOpen; 2023. doi: 10.5772/intechopen.104142. [cited 2025 Dec 15]. Available from: https://www.intechopen. com/chapters/86816.

Oladele RO, Ayanlowo OO, Richardson MD, Denning DW. Histoplasmosis in Africa: An emerging or a neglected disease? PLoS Negl Trop Dis. 2018;12(1):e0006046. doi: 10.1371/journal.pntd.0006046.

Baker J, Setianingrum F, Wahyuningsih R, Denning DW. Mapping histoplasmosis in South East Asia – implications for diagnosis in AIDS. Emerg Microbes Infect. 2019;8(1):1139-45. doi: 10.1080/22221751.2019.1644539.

Rodrigues AM, Beale MA, Hagen F, Fisher MC, Terra PPD, de Hoog S, et al. The global epidemiology of emerging Histoplasma species in recent years. Stud Mycol. 2020;97:100095. doi: 10.1016/j.simyco.2020.02.001.

Ekeng BE, Edem K, Akintan P, Oladele RO. Histoplasmosis in African children: clinical features, diagnosis and treatment. Ther Adv Infect Dis. 2022;9:20499361211068592. doi: 10.1177/20499361211068592.

Knox KS, Hage CA. Histoplasmosis. Proc Am Thorac Soc. 2010;7(3):169-72. doi: 10.1513/pats.200907-069AL.

Ekeng BE, Oladele RO, Emanghe UE, Ochang EA, Mirabeau TY. Prevalence of Histoplasmosis and Molecular Characterization of Histoplasma species in Patients with Presumptive Pulmonary Tuberculosis in Calabar, Nigeria. Open Forum Infect Dis. 2022;9(8):ofac368. doi: 10.1093/ ofid/ofac368.

Guimarães AJ, de Cerqueira MD, Nosanchuk JD. Surface Architecture of Histoplasma Capsulatum. Front Microbiol. 2011;2:225. doi: 10.3389/fmicb.2011.00225.

Lara-Lemus R, Alvarado-Vásquez N, Zenteno E, Gorocica P. Effect of Histoplasma capsulatum glucans on host innate immunity. Rev Iberoam Micol. 2014;31(1):76-80. doi: 10.1016/j.riam.2013.10.005.

Bernard M, Latgé JP. Aspergillus fumigatus cell wall: composition and biosynthesis. Med Mycol. 2001;39 Suppl 1:9-17. doi: 10.1080/714030981.

Borges-Walmsley MI, Chen D, Shu X, Walmsley AR. The pathobiology of Paracoccidioides brasiliensis. Trends Microbiol. 2002;10(2):80-7. doi: 10.1016/s0966-842x(01)02292-2.

Eissenberg LG, Goldman WE. Histoplasma variation and adaptive strategies for parasitism: new perspectives on histoplasmosis. Clin Microbiol Rev. 1991;4(4):411–21. doi: 10.1128/CMR.4.4.411.

Santos GMP dos, Santos GRC dos, Xisto MID da S, Rollin-Pinheiro R, Baptista AR de S, Rocha EM da S da, et al. Peptidogalactomannan from Histoplasma capsulatum yeast cell wall: role of the chemical structure in recogni- tion and activation by peritoneal macrophages. Braz J Microbiol. 2021;52(2):479. doi: 10.1007/s42770-021-00447-w.

Kroetz DN, George S Deepe J. The role of cytokines and chemokines in Histoplasma capsulatum infection. Cytokine. 2011;58(1):112. doi: 10.1016/j.cyto.2011.07.430.

Taylor ML, Duarte-Escalante E, Pérez A, Zenteno E, Toriello C. Histoplasma capsulatum yeast cells at- tach and agglutinate human erythrocytes. Med Mycol. 2004;42(3):287-92. doi: 10.1080/13693780310001644734.

Maresca B, Kobayashi GS. Dimorphism in Histoplasma capsulatum: a model for the study of cell differentiation in pathogenic fungi. Microbiol Rev. 1989;53(2):186-209. doi: 10.1128/mr.53.2.186-209.1989.

Zancopé-Oliveira RM, Reiss E, Lott TJ, Mayer LW, Deepe GS. Molecular cloning, characterization, and expression of the M antigen of Histoplasma capsulatum. Infect Immun. 1999;67(4):1947-53. doi: 10.1128/IAI.67.4.1947-1953.1999.

Deepe GS, Durose GG. Immunobiological activity of recombinant H antigen from Histoplasma capsulatum. Infect Immun. 1995;63(8):3151-7. doi: 10.1128/ iai.63.8.3151-3157.1995.

Guimarães AJ, Hamilton AJ, de M. Guedes HL, Nosanchuk JD, Zancopé-Oliveira RM. Biological Function and Molecular Mapping of M Antigen in Yeast Phase of His- toplasma capsulatum. PLoS ONE. 2008;3(10):e3449. doi: 10.1371/journal.pone.0003449.

Cleare LG, Zamith D, Heyman HM, Couvillion SP, Nimrichter L, Rodrigues ML, et al. Media matters! Alterations in the loading and release of Histoplasma capsulatum extracellular vesicles in response to different nutritional milieus. Cell Microbiol. 2020;22(9):e13217. doi: 10.1111/ cmi.13217.

Baltazar LM, Zamith-Miranda D, Burnet MC, Choi H, Nimrichter L, Nakayasu ES, et al. Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages. Sci Rep. 2018;8:8065. doi: 10.1038/s41598-018-25665-5.

Taborda CP, da Silva MB, Nosanchuk JD, Travassos LR. Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview. Mycopathologia. 2008;165(4-5):331-9. doi: 10.1007/s11046-007-9061-4.

Duin D van, Casadevall A, Nosanchuk JD. Melaniza- tion of Cryptococcus neoformans and Histoplasma capsulatum Reduces Their Susceptibilities to Ampho- tericin B and Caspofungin. Antimicrob Agents Chemother. 2002;46(11):3394. doi: 10.1128/AAC.46.11.3394-3400.2002.

Eisenman HC, Greer EM, McGrail CW. The role of melanins in melanotic fungi for pathogenesis and environmental survival. Appl Microbiol Biotechnol. 2020;104(10):4247-57. doi: 10.1007/s00253-020-10532-z.

Bullock WE, Wright SD. Role of the adherence-promoting receptors, CR3, LFA-1, and p150,95, in binding of Histoplasma capsulatum by human macrophages. J Exp Med. 1987;165(1):195-210. doi: 10.1084/jem.165.1.195.

Long KH, Gomez FJ, Morris RE, Newman SL. Identification of heat shock protein 60 as the ligand on Histoplasma capsulatum that mediates binding to CD18 receptors on human macrophages. J Immunol Baltim Md 1950. 2003;170(1):487-94. doi: 10.4049/jimmunol.170.1.487.

Aravalli RN, Hu S, Woods JP, Lokensgard JR. Histoplasma capsulatum yeast phase-specific protein Yps3p induces Toll-like receptor 2 signaling. J Neuroinflammation. 2008;5:30. doi: 10.1186/1742-2094-5-30.

Youseff BH, Holbrook ED, Smolnycki KA, Rappleye CA. Extracellular superoxide dismutase protects Histoplasma yeast cells from host-derived oxidative stress. PLoS Pathog. 2012;8(5):e1002713. doi: 10.1371/journal. ppat.1002713.

Dos Santos GMP, Dos Santos GRC, Xisto MIDDS, Rollin-Pinheiro R, Baptista ARDS, Da Rocha EMDS, et al. Pep- tidogalactomannan from Histoplasma capsulatum yeast cell wall: role of the chemical structure in recognition and activation by peritoneal macrophages. Braz J Microbiol. 2021;52(2):479-89. doi: 10.1007/s42770-021-00447-w.

Ganz T. Macrophages and Iron Metabolism. Microbiol Spectr. 2016;4(5). doi: 10.1128/microbiolspec.MCHD-0037-2016.

Shen Q, Beucler MJ, Ray SC, Rappleye CA. Macrophage activation by IFN-γ triggers restriction of phagosomal copper from intracellular pathogens. Lin X, editor. PLOS Pathog. 2018;14(11):e1007444. doi: 10.1371/journal. ppat.1007444.

Gildea LA, Morris RE, Newman SL. Histoplasma capsulatum Yeasts Are Phagocytosed Via Very Late Antigen-5, Killed, and Processed for Antigen Presentation by Human Dendritic Cells. J Immunol. 2001;166(2):1049-56. doi: 10.4049/jimmunol.166.2.1049.

Honda TSB, Ku J, Anders HJ. Cell type-specific roles of NLRP3, inflammasome-dependent and -independent, in host defense, sterile necroinflammation, tissue repair, and fibrosis. Front Immunol. 2023;14:1214289. doi: 10.3389/ fimmu.2023.1214289.

Valdez AF, Miranda DZ, Guimarães AJ, Nimrichter L, Nosanchuk JD. Pathogenicity & virulence of Histoplasma capsulatum - A multifaceted organism adapted to intracellular environments. Virulence. 2022;13(1):2137987. doi: 10.1080/21505594.2022.2137987.

Ray SC, Rappleye CA. Flying under the radar: Histoplasma capsulatum avoidance of innate immune recogni- tion. Semin Cell Dev Biol. 2019;89:91-8. doi: 10.1016/j. semcdb.2018.03.009.

Newman SL, Gootee L, Gabay JE. Human neutrophil-mediated fungistasis against Histoplasma capsulatum. Local- ization of fungistatic activity to the azurophil granules. J Clin Invest. 1993;92(2):624-31. doi: 10.1172/JCI116630.

Thompson-Souza GA, Santos GMP, Silva JC, Muniz VS, Braga YAV, Figueiredo RT, et al. Histoplasma capsulatum-induced extracellular DNA trap release in human neutrophils. Cell Microbiol. 2020;22(7):e13195. doi: 10.1111/ cmi.13195.

Newman SL, Gootee L, Gabay JE, Selsted ME. Identifi- cation of Constituents of Human Neutrophil Azurophil Granules That Mediate Fungistasis against Histoplasma capsulatum. Infect Immun. 2000;68(10):5668-72. doi: 10.1128/IAI.68.10.5668-5672.2000.

Beyhan S, Sil A. Sensing the heat and the host: Virulence determinants of Histoplasma capsulatum. Virulence. 2019;10(1):793-800.doi:10.1080/21505594.2019.1663596.

Lee GR. Molecular Mechanisms of T Helper Cell Differentiation and Functional Specialization. Immune Netw [Internet]. 2023;23(1). doi: 10.4110/in.2023.23.e4. [cited 2025 July 21]. Available from: https://immunenetwork. org/DOIx.php?id=10.4110/in.2023.23.e4.

Clemons KV, Darbonne WC, Curnutte JT, Sobel RA, Ste- vens DA. Experimental histoplasmosis in mice treated with anti-murine interferon-γ antibody and in interferon-γ gene knockout mice. Microbes Infect. 2000;2(9):997-1001. doi: 10.1016/s1286-4579(00)01253-3.

Kroetz DN, Deepe GS. The role of cytokines and chemokines in Histoplasma capsulatum infection. Cytokine. 2012;58(1):112-7. doi: 10.1016/j.cyto.2011.07.430.

Heninger E, Hogan LH, Karman J, Macvilay S, Hill B, Woods JP, et al. Characterization of the Histoplasma capsulatum-Induced Granuloma. J Immunol. 2006;177(5):3303-13. doi: 10.4049/jimmunol.177.5.3303.

Wüthrich M, Gern B, Hung CY, Ersland K, Rocco N, Pick-Jacobs J, et al. Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J Clin Invest. 2011;121(2):554-68. doi: 10.1172/JCI43984.

Allen HL, Deepe GS. B Cells and CD4−CD8− T Cells Are Key Regulators of the Severity of Reactivation Histoplasmosis. J Immunol. 2006;177(3):1763-71. doi: 10.4049/ jimmunol.177.3.1763.

Nosanchuk JD, Zancopé-Oliveira RM, Hamilton AJ, Guimarães AJ. Antibody Therapy for Histoplasmosis. Front Microbiol [Internet]. 2012;3. doi: 10.3389/ fmicb.2012.00021. [cited 2025 Jan 14]. Available from: http://journal.frontiersin.org/article/10.3389/ fmicb.2012.00021/abstract.

Nemecek JC, Wüthrich M, Klein BS. Global control of dimorphism and virulence in fungi. Science. 2006;312(5773):583-8. doi: 10.1126/science.1124105.

Scherr GH. Studies on the dimorphism of Histoplasma capsulatum: I. The roles of -SH groups and incubation temperature. Exp Cell Res. 1957;12(1):92-107. doi: 10.1016/0014-4827(57)90296-3.

Pine L. Studies on the Growth of Histoplasma capsulatum I. Growth of the Yeast Phase in Liquid Media. J Bacteriol. 1954;68(6):671-9. doi: 10.1128/jb.68.6.671-679.1954.

Sacco M, Medoff G, Lambowitz A, Kumar B, Kobayashi G, Painter A. Sulphydryl induced respiratory ‘shunt’ pathways and their role in morphogenesis in the fungus Histo- plasma capsulatum. J Biol Chem. 1983;258:8223-30. doi: 10.1016/S0021-9258(20)82052-3.

Surja SS, Kurniawan AJ, Wilyani R, Adawiyah R, Kaisar MMM, Wahyuningsih R. First morphological description of Histoplasma capsulatum Indonesian strain: Successful yeast phase conversion. Microbes Infect Dis [Internet]. 2025 Feb 1. doi: 10.21608/mid.2025.340492.2375. [cited 2025 Aug 17]; Available from: https://mid.journals.ekb.eg/article_409408.html.

Maresca B, Lambowitz AM, Kumar VB, Grant GA, Ko- bayashi GS, Medoff G. Role of cysteine in regulating morphogenesis and mitochondrial activity in the dimorphic fungus Histoplasma capsulatum. Proc Natl Acad Sci U S A. 1981;78(7):4596-600. doi: 10.1073/pnas.78.7.4596.

Shen Q, Rappleye CA. Differentiation of the fungus Histoplasma capsulatum into a pathogen of phagocytes. Curr Opin Microbiol. 2017;40:1-7. doi: 10.1016/j. mib.2017.10.003.

Rappleye CA, Eissenberg LG, Goldman WE. Histoplasma capsulatum α-(1,3)-glucan blocks innate immune rec- ognition by the β-glucan receptor. Proc Natl Acad Sci. 2007;104(4):1366-70. doi: 10.1073/pnas.0609848104.

Garfoot AL, Shen Q, Wüthrich M, Klein BS, Rappleye CA. The Eng1 β-Glucanase Enhances Histoplasma Virulence by Reducing β-Glucan Exposure. mBio. 2016;7(2):e01388-15. doi: 10.1128/mBio.01388-15.

Holbrook ED, Smolnycki KA, Youseff BH, Rappleye CA. Redundant Catalases Detoxify Phagocyte Reactive Oxygen and Facilitate Histoplasma capsulatum Pathogenesis. Infect Immun. 2013;81(7):2334-46. doi: 10.1128/IAI.00173-13

Wangsanut T, Pongpom M. The Role of the Gluta- thione System in Stress Adaptation, Morphogenesis and Virulence of Pathogenic Fungi. Int J Mol Sci. 2022;23(18):10645. doi: 10.3390/ijms231810645.

DuBois JC, Smulian AG. Sterol Regulatory Element Binding Protein (Srb1) Is Required for Hypoxic Adaptation and Virulence in the Dimorphic Fungus Histoplasma capsulatum. PLOS ONE. 2016;11(10):e0163849. doi: 10.1371/journal.pone.0163849.

Hwang LH, Seth E, Gilmore SA, Sil A. SRE1 Regulates Iron-Dependent and -Independent Pathways in the Fun- gal Pathogen Histoplasma capsulatum. Eukaryot Cell. 2012;11(1):16-25. doi: 10.1128/EC.05274-11.

Hilty J, George Smulian A, Newman SL. Histoplasma capsulatum utilizes siderophores for intracellular iron acquisition in macrophages. Med Mycol. 2011;1-10. doi: 10.3109/13693786.2011.558930.

Subramanian Vignesh K, Landero Figueroa JA, Porollo A, Caruso JA, Deepe GS. Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival. Immunity. 2013;39(4):697-710. doi: 10.1016/j. immuni.2013.09.006.

Dade J, DuBois JC, Pasula R, Donnell AM, Caruso JA, Smulian AG, et al. HcZrt2, a zinc responsive gene, is indispensable for the survival of Histoplasma capsulatum in vivo. Med Mycol. 2016;54(8):865-75. doi: 10.1093/mmy/ myw045.

Ray SC, Rappleye CA. Mac1-Dependent Copper Sensing Promotes Histoplasma Adaptation to the Phagosome during Adaptive Immunity. mBio. 2022;13(2):e03773-21. doi: 10.1128/mbio.03773-21.

Shen Q, Ray SC, Evans HM, Deepe GS, Rappleye CA. Metabolism of Gluconeogenic Substrates by an Intracellular Fungal Pathogen Circumvents Nutritional Limitations within Macrophages. mBio. 2020;11(2):e02712-19. doi: 10.1128/mBio.02712-19.

Shen Q, Gonzalez-Mireles A, Ray SC, Rappleye CA. His- toplasma capsulatum Relies on Tryptophan Biosynthesis To Proliferate within the Macrophage Phagosome. Infect Immun. 2023;91(6):e00059-23. doi: 10.1128/iai.00059-23.

Garfoot AL, Zemska O, Rappleye CA. Histoplasma capsulatum Depends on De Novo Vitamin Biosynthesis for Intraphagosomal Proliferation. Infect Immun. 2014;82(1):393-404. doi: 10.1128/IAI.00824-13.

Isaac DT, Berkes CA, English BC, Murray DH, Lee YN, Coady A, et al. Macrophage cell death and transcriptional response are actively triggered by the fungal virulence factor Cbp1 during H. capsulatum infection. Mol Microbiol. 2015;98(5):910-29. doi: 10.1111/mmi.13168.

English BC, Van Prooyen N, Örd T, Örd T, Sil A. The transcription factor CHOP, an effector of the integrated stress response, is required for host sensitivity to the fungal intracellular pathogen Histoplasma capsulatum. PLOS Pathog. 2017;13(9):e1006589. doi: 10.1371/journal. ppat.1006589.

Azimova D, Herrera N, Duvenage L, Voorhies M, Rodriguez RA, English BC, et al. Cbp1, a fungal virulence factor under positive selection, forms an effector complex that drives macrophagelysis. PLOS Pathog.

2022;18(6):e1010417. doi: 10.1371/journal.ppat.1010417.

Shen Q, Steinmetz K. Elevated carbon dioxide enhances the growth and reduces the antifungal susceptibility of Histoplasma capsulatum. Microbiol Spectr. 2025;13(7):e03106-24. doi: 10.1128/spectrum.03106-24.

Schnizlein-bick C, Durkin M, Kohler S, Connolly P, LeM- onte A, Garringer T, et al. Effects of CD4 and CD8 T lymphocyte depletion on the course of histoplasmosis following pulmonary challenge. Med Mycol. 2003;41(3):189-97. doi: 10.1080/1369378031000137279.

Nightingale SD, Parks JM, Pounders SM, Burns DK, Reynolds J, Hernandez JA. Disseminated histoplasmosis in patients with AIDS. South Med J. 1990;83(6):624-30. doi: 10.1097/00007611-199006000-00007.

Wright T, Coruh B, Fredricks D, Kim N. Immune reconstitution inflammatory syndrome associated with disseminated histoplasmosis and TNF-alpha inhibi- tion. Med Mycol Case Rep. 2019;23:62-4. doi: 10.1016/j. mmcr.2018.12.008.

Azar MM, Hage CA. Laboratory Diagnostics for Histo- plasmosis. J Clin Microbiol. 2017;55(6):1612-20. doi: 10.1128/JCM.02430-16.

Hage CA, Ribes JA, Wengenack NL, Baddour LM, Assi M, McKinsey DS, et al. A multicenter evaluation of tests for diagnosis of histoplasmosis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2011;53(5):448-54. doi: 10.1093/cid/ cir435.

Villareal K, Price A, Pasqualotto AC, Bahr NC. The Current and Future States of Diagnostic Tests for Histoplas- mosis with a Focus on People with HIV and Disseminated Histoplasmosis. J Fungi Basel Switz. 2023;9(8):793. doi: 10.3390/jof9080793.

Datta K, LaRue R, Permpalung N, Das S, Zhang S, Mehta Steinke S, et al. Development of an Interferon-Gamma Release Assay (IGRA) to Aid Diagnosis of Histoplasmo- sis. J Clin Microbiol. 2022;60(10):e0112822. doi: 10.1128/ jcm.01128-22.

Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKin- sey DS, Loyd JE, et al. Clinical Practice Guidelines for the Management of Patients with Histoplasmosis: 2007 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45(7):807-25. doi: 10.1086/521259.

Arnold SR, Spec A, Baddley JW, Pappas P, Lentz RJ, Wolf J, et al. 2025 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Histoplasmosis: Treatment of Asymptomatic Histoplasma Pulmonary Nodules (Histoplasmomas) and Mild or Moderate Acute Pulmonary Histoplasmosis in Adults, Children, and Pregnant People. Clin Infect Dis. 2025;ciaf256. doi: 10.1093/ cid/ciaf256.

Deepe GS, Buesing WR, Ostroff GR, Abraham A, Specht CA, Huang H, et al. Vaccination with an alkaline extract of Histoplasma capsulatum packaged in glucan particles confers protective immunity in mice. Vaccine. 2018;36(23):3359-67. doi: 10.1016/j.vaccine.2018.04.047.

Roth MT, Zamith-Miranda D, Nosanchuk JD. Immuni- zation Strategies for the Control of Histoplasmosis. Curr Trop Med Rep. 2019;6(2):35–41. doi: 10.1007/s40475-019-00172-3.

Almeida PCS, Roque BS, Felice AG, Jaiswal AK, Tiwari S, Azevedo V, et al. Comparative Genomics of Histoplasma capsulatum and Prediction of New Vaccines and Drug Targets. J Fungi Basel Switz. 2023;9(2):193. doi: 10.3390/ jof9020193.

Sepúlveda VE, Márquez R, Turissini DA, Goldman WE, Matute DR. Genome Sequences Reveal Cryptic Speciation in the Human Pathogen Histoplasma capsulatum. mBio. 2017;8(6):e01339-17. doi: 10.1128/mBio.01339-17.

Sepúlveda VE, Rader JA, Li JJ, Goldman WE, Matute DR. Phenotypic characterization of cryptic species in the fungal pathogen Histoplasma. mSphere. 2024;9(6):e0000924. doi: 10.1128/msphere.00009-24.

Almeida-Silva F, de Melo Teixeira M, Matute DR, de Faria Ferreira M, Barker BM, Almeida-Paes R, et al. Genomic Diversity Analysis Reveals a Strong Population Structure in Histoplasma capsulatum LAmA (Histoplasma suramericanum). J Fungi Basel Switz. 2021;7(10):865. doi: 10.3390/jof7100865.

Quan Y, Zhou X, Belmonte-Lopes R, Li N, Wahyuning- sih R, Chowdhary A, et al. Potential predictive value of phylogenetic novelties in clinical fungi, illustrated by His- toplasma. IMA Fungus. 2025;16:e145658. doi: 10.3897/ imafungus.16.145658.

Araúz AB, Papineni P. Histoplasmosis. Infect Dis Clin North Am. 2021;35(2):471-91. doi: 10.1016/j.idc.2021.03.011.

Hsu JC, Chang PH, Tai CH, Chen YC. Histoplasmosis in Taiwan: Case Summary and Literature Review. Life. 2024;14(6):738. doi: 10.3390/life14060738.

Rahim MA, Zaman S, Amin MR, Uddin KN, Ma JC. Histoplasmosis: An Emerging or Neglected Disease in Bangladesh? A Systematic Review. Oman Med J. 2020;35(1):e91. doi: 10.5001/omj.2020.09.

Thapa S, Jha SC, Trotter AB. Persistent Fever and Skin Lesions Due to Histoplasmosis in a Boy from Rural Nepal. Am J Trop Med Hyg. 2016;94(2):249-50. doi: 10.4269/ ajtmh.15-0664.

Ocansey BK, Kosmidis C, Agyei M, Dorkenoo AM, Ayanlowo OO, Oladele RO, et al. Histoplasmosis in Africa: Current perspectives, knowledge gaps, and research priorities. PLoS Negl Trop Dis. 2022;16(2):e0010111. doi: 10.1371/journal.pntd.0010111.

Downloads

Published

31.12.2025

Issue

Section

Clinical Medicine

How to Cite

How Histoplasma Evades the Human Immune System. (2025). Acta Medica Academica, 54(3), 220-237. https://doi.org/10.5644/ama2006-124.494

Most read articles by the same author(s)