Dataset Information

IL-17 Production of Neutrophils Enhances Antibacteria Ability but Promotes Arthritis Development During Mycobacterium tuberculosis Infection.

ABSTRACT: To our knowledge, no studies have examined the role of IL-17 production by neutrophils in immune defense against Mycobacterium tuberculosis (MTB) infection and the pathogenesis of rheumatoid arthritis (RA) caused by MTB infection. Here, we determined that neutrophils express IL-17 in an autocrine IL-6- and IL-23-dependent manner during MTB infection. MTB H37Rv-induced IL-6 production was dependent on the NF-?B, p38, and JNK signaling pathways; however, IL-23 production was dependent on NF-?B and EKR in neutrophils. Furthermore, we found that Toll-like receptor 2 (TLR2) and TLR4 mediated the activation of the kinases NF-?B, p38, ERK, and JNK and the production of IL-6, IL-23, and IL-17 in neutrophils infected with MTB H37Rv. Autocrine IL-17 produced by neutrophils played a vital role in inhibiting MTB H37Rv growth by mediating reactive oxygen species production and the migration of neutrophils in the early stages of infection. However, IL-17 production by neutrophils contributed to collagen-induced arthritis development during MTB infection. Our findings identify a protective mechanism against mycobacteria and the pathogenic role of MTB in arthritis development.

SUBMITTER: Hu S

PROVIDER: S-EPMC5605331 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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IL-17 Production of Neutrophils Enhances Antibacteria Ability but Promotes Arthritis Development During Mycobacterium tuberculosis Infection.

Hu Shengfeng S He Wenting W Du Xialin X Yang Jiahui J Wen Qian Q Zhong Xiao-Ping XP Ma Li L

EBioMedicine 20170809

To our knowledge, no studies have examined the role of IL-17 production by neutrophils in immune defense against Mycobacterium tuberculosis (MTB) infection and the pathogenesis of rheumatoid arthritis (RA) caused by MTB infection. Here, we determined that neutrophils express IL-17 in an autocrine IL-6- and IL-23-dependent manner during MTB infection. MTB H37Rv-induced IL-6 production was dependent on the NF-κB, p38, and JNK signaling pathways; however, IL-23 production was dependent on NF-κB and ...[more]

PMID: 28821374

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Project description:Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one third of the world's population. Among these infections, clinical isolates belonging to the W-Beijing appear to be emerging, representing about 50% of Mtb isolates in East Asia, and about 13% of all Mtb isolates worldwide. In animal models, infection with W-Beijing strain, Mtb HN878, is considered "hypervirulent" as it results in increased mortality and causes exacerbated immunopathology in infected animals. We had previously shown the Interleukin (IL) -17 pathway is dispensable for primary immunity against infection with the lab adapted Mtb H37Rv strain. However, it is not known whether IL-17 has any role to play in protective immunity against infection with clinical Mtb isolates. We report here that lab adapted Mtb strains, such as H37Rv, or less virulent Mtb clinical isolates, such as Mtb CDC1551, do not require IL-17 for protective immunity against infection while infection with Mtb HN878 requires IL-17 for early protective immunity. Unexpectedly, Mtb HN878 induces robust production of IL-1β through a TLR-2-dependent mechanism, which supports potent IL-17 responses. We also show that the role for IL-17 in mediating protective immunity against Mtb HN878 is through IL-17 Receptor signaling in non-hematopoietic cells, mediating the induction of the chemokine, CXCL-13, which is required for localization of T cells within lung lymphoid follicles. Correct T cell localization within lymphoid follicles in the lung is required for maximal macrophage activation and Mtb control. Since IL-17 has a critical role in vaccine-induced immunity against TB, our results have far reaching implications for the design of vaccines and therapies to prevent and treat emerging Mtb strains. In addition, our data changes the existing paradigm that IL-17 is dispensable for primary immunity against Mtb infection, and instead suggests a differential role for IL-17 in early protective immunity against emerging Mtb strains.

Dataset Information

IL-17 Production of Neutrophils Enhances Antibacteria Ability but Promotes Arthritis Development During Mycobacterium tuberculosis Infection.

Publications

IL-17 Production of Neutrophils Enhances Antibacteria Ability but Promotes Arthritis Development During Mycobacterium tuberculosis Infection.

Similar Datasets

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