Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

PLoS Pathogens

Nelson L. Michael¹  Lynn Soong²  Sarah Auclair²  Jiaren Sun²  Xiuzhen Fan²  Fengliang Liu²  Monique Ferguson³  Robert R. Redfield⁴  Jerome H. Kim⁵  Wei Hou⁶  Silvia Ratto-Kim⁷  Merlin L. Robb⁷  Haitao Hu⁸  Deborah L. Birx⁸ 

[1] U.S. Military HIV Research Program, Water Reed Army Institute of Research, Silver Spring, Maryland, United States of America;Department of Microbiology & Immunology and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, United States of America;Division of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America;Institute of Human Virology and Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, Maryland, United States of America;International Vaccine Institute, Seoul, Republic of Korea;School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China;U.S. Military HIV Research Program, Henry M. Jackson Foundation, Silver Spring, Maryland, United States of America;U.S. Military HIV Research Program, Water Reed Army Institute of Research, Silver Spring, Maryland, United States of America

关键词: T helper cells;    HIV;    HIV infections;    T cells;    C;    ida albicans;    Cytokines;    Cell-mediated immunity;    Immune response;   

DOI  :  10.1371/journal.ppat.1005663

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.

【 授权许可】

CC BY