Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Infect Immun. 2020 Jul 21;88(8). doi: 10.1128/IAI.00026-20.
The intracellular bacterial pathogen is able to evade the immune system and persist within the host. In some cases, these persistent infections are asymptomatic for long periods and represent a significant public health hazard because the hosts are potential chronic carriers, yet the mechanisms that control persistence are incompletely understood. Using a mouse model of chronic typhoid fever combined with major histocompatibility complex (MHC) class II tetramers to interrogate endogenous, -specific CD4 helper T cells, we show that certain host microenvironments may favorably contribute to a pathogen's ability to persist We demonstrate that the environment in the hepatobiliary system may contribute to the persistence of subsp. serovar Typhimurium through liver-resident immunoregulatory CD4 helper T cells, alternatively activated macrophages, and impaired bactericidal activity. This contrasts with lymphoid organs, such as the spleen and mesenteric lymph nodes, where these same cells appear to have a greater capacity for bacterial killing, which may contribute to control of bacteria in these organs. We also found that, following an extended period of infection of more than 2 years, the liver appeared to be the only site that harbored bacteria. This work establishes a potential role for nonlymphoid organ immunity in regulating chronic bacterial infections and provides further evidence for the hepatobiliary system as the site of chronic infection.
胞内细菌病原体能够逃避免疫系统并在宿主体内持续存在。在某些情况下，这些持续感染会在很长一段时间内无症状，并且构成重大的公共卫生危害，因为宿主可能是潜在的慢性携带者，但控制持续性的机制尚不完全清楚。本研究使用慢性伤寒小鼠模型结合主要组织相容性复合物（MHC）II 类四聚体来探究内源性、特异性 CD4 辅助 T 细胞，结果表明某些宿主微环境可能有利于病原体的持续性。本研究证明，肝胆系统的环境可能通过肝脏固有免疫调节性 CD4 辅助 T 细胞、交替激活的巨噬细胞和杀菌活性受损，促进副伤寒沙门氏菌血清型 Typhimurium 的持续存在。这与淋巴器官（如脾脏和肠系膜淋巴结）形成对比，在这些器官中，相同的细胞似乎具有更强的杀菌能力，这可能有助于控制这些器官中的细菌。本研究还发现，在超过 2 年的长期感染后，肝脏似乎是唯一携带细菌的部位。这项工作确立了非淋巴器官免疫在调节慢性细菌感染中的潜在作用，并为肝胆系统作为慢性感染部位提供了进一步的证据。
