Chronic viral infection impairs immune memory to a different pathogen

作者全名："Yang, Cheng; Liu, Zhicui; Yang, Ying; Cocka, Luis J.; Li, Yongguo; Zeng, Weihong; Shen, Hao"

作者地址："[Yang, Cheng; Li, Yongguo] Chongqing Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing, Peoples R China; [Yang, Cheng; Liu, Zhicui; Yang, Ying; Cocka, Luis J.; Zeng, Weihong; Shen, Hao] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA; [Liu, Zhicui] Tongji Univ, Shanghai Peoples Hosp 10, Dept Dermatol, Sch Med, Shanghai, Peoples R China; [Yang, Ying] Hainan Med Univ, Hainan Acad Med Sci, Hainan, Peoples R China; [Zeng, Weihong] Shanghai Jiao Tong Univ, Int Peace Matern & Child Hlth Hosp, Shanghai Key Lab Embryo Original Dis, Sch Med, Shanghai, Peoples R China"

通信作者："Li, YG (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing, Peoples R China.; Zeng, WH; Shen, H (通讯作者)，Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.; Zeng, WH (通讯作者)，Shanghai Jiao Tong Univ, Int Peace Matern & Child Hlth Hosp, Shanghai Key Lab Embryo Original Dis, Sch Med, Shanghai, Peoples R China."

来源：PLOS PATHOGENS

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001194706800002

JCR分区：Q1

影响因子：6.7

年份：2024

卷号：20

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Chronic viral infections cause T cell dysfunction in both animal models and human clinical settings, thereby affecting the ability of the host immune system to clear viral pathogens and develop proper virus-specific immune memory. However, the impact of chronic viral infections on the host's immune memory to other pathogens has not been well described. In this study, we immunized mice with recombinant Listeria monocytogenes expressing OVA (Lm-OVA) to generate immunity to Lm and allow analysis of OVA-specific memory T (Tm) cells. We then infected these mice with lymphocytic choriomeningitis virus (LCMV) strain Cl-13 which establishes a chronic infection. We found that chronically infected mice were unable to protect against Listeria re-challenge. OVA-specific Tm cells showed a progressive loss in total numbers and in their ability to produce effector cytokines in the context of chronic LCMV infection. Unlike virus-specific T cells, OVA-specific Tm cells from chronically infected mice did not up-regulate the expression of inhibitory receptors, a hallmark feature of exhaustion in virus-specific T cells. Finally, OVA-specific Tm cells failed to mount a robust recall response after bacteria re-challenge both in the chronically infected and adoptively transferred naive hosts. These results show that previously established bacteria-specific Tm cells become functionally impaired in the setting of an unrelated bystander chronic viral infection, which may contribute to poor immunity against other pathogens in the host with chronic viral infection. The impact of chronic viral infections on protective immunity to other pathogens remains largely unknown. Our data showed that mice infected with a chronic virus were incapable of conferring protection against bacterial reinfection. Mechanistically, infection by chronic virus not only reduced the number of bacterial-specific memory T cells, but also led to dysfunction of these cells as evident by diminished production of effector molecules and poor recall responses. Our results provide novel insights into immune mechanisms underlying the increased susceptibility to other pathogens in chronic virus infected hosts."

基金机构：National Institute of Health; NIH

基金资助正文："We thank members of Shen lab for their assistance in conducting this research, and NIH Tetramer Core Facility for providing tetramers."