ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Deciphering the pathways of death of Histoplasma capsulatum-infected macrophages: implications for the immunopathogenesis of early infection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- The use of genetic markers in the molecular epidemiology of histoplasmosis: a systematic review.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2016Pooled it
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- Statins: a viable candidate for host-directed therapy against infectious diseases.Nature reviews. Immunology · 2019Review
- Histoplasma Capsulatum: Mechanisms for Pathogenesis.Current topics in microbiology and immunology · 2019Review
- IL-1R and Inflammasomes Mediate Early Pulmonary Protective Mechanisms in RespiratoryFrontiers in cellular and infection microbiology · 2018Article
- Non-Neutralizing Antibodies Directed against HIV and Their Functions.Frontiers in immunology · 2017Review
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- Revisiting old friends: Developments in understanding Histoplasma capsulatum pathogenesis.Journal of microbiology (Seoul, Korea) · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Apoptosis of leukocytes is known to strongly influence the immunopathogenesis of infection. In this study, we dissected the death pathways of murine macrophages (MΦs) infected with the intracellular pathogen Histoplasma capsulatum. Yeast cells caused apoptosis of MΦs at a wide range of multiplicity of infection, but smaller inocula resulted in delayed detection of apoptosis. Upon infection, caspases 3 and 1 were activated, and both contributed to cell death; however, only the former was involved in apoptosis. The principal driving force for apoptosis involved the extrinsic pathway via engagement of TNFR1 by TNF-α. Infected MΦs produced IL-10 that dampened apoptosis. The chronology of TNF-α and IL-10 release differed in vitro. The former was detected by 2 h postinfection, and the latter was not detected until 8 h postinfection. In vivo, the lungs of TNFR1(-/-) mice infected for 1 d contained fewer apoptotic MΦs than wild-type mice, whereas the lungs of IL-10(-/-) mice exhibited more. Blockade of apoptosis by a pan-caspase inhibitor or by simvastatin sharply reduced the release of TNF-α but enhanced IL-10. However, these treatments did not modify the fungal burden in vitro over 72 h. Thus, suppressing cell death modulated cytokine release but did not alter the fungal burden. These findings provide a framework for the early pathogenesis of histoplasmosis in which yeast cell invasion of lung MΦs engenders apoptosis, triggered in part in an autocrine TNF-α-dependent manner, followed by release of IL-10 that likely prevents apoptosis of newly infected neighboring phagocytes.
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Registered trials
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