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Mammary γδ T cells promote IL-17A-mediated immunity against Staphylococcus aureus-induced mastitis in a microbiota-dependent manner.

ABSTRACT: Mastitis, a common disease for female during lactation period that could cause a health risk for human or huge economic losses for animals, is mainly caused by S. aureus invasion. Here, we found that neutrophil recruitment via IL-17A-mediated signaling was required for host defense against S. aureus-induced mastitis in a mouse model. The rapid accumulation and activation of Vγ4⁺ γδ T cells in the early stage of infection triggered the IL-17A-mediated immune response. Interestingly, the accumulation and influence of γδT17 cells in host defense against S. aureus-induced mastitis in a commensal microbiota-dependent manner. Overall, this study, focusing on γδT17 cells, clarified innate immune response mechanisms against S. aureus-induced mastitis, and provided a specific response to target for future immunotherapies. Meanwhile, a link between commensal microbiota community and host defense to S. aureus mammary gland infection may unveil potential therapeutic strategies to combat these intractable infections.

SUBMITTER: Pan N

PROVIDER: S-EPMC10687336 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Mammary γδ T cells promote IL-17A-mediated immunity against Staphylococcus aureus-induced mastitis in a microbiota-dependent manner.

Pan Na N Xiu Lei L Xu Ying Y Bao Xuemei X Liang Yanchen Y Zhang Haochi H Liu Bohui B Feng Yuanyu Y Guo Huibo H Wu Jing J Li Haotian H Ma Cheng C Sheng Shouxin S Wang Ting T Wang Xiao X

iScience 20231114 12

Mastitis, a common disease for female during lactation period that could cause a health risk for human or huge economic losses for animals, is mainly caused by S. aureus invasion. Here, we found that neutrophil recruitment via IL-17A-mediated signaling was required for host defense against S. aureus-induced mastitis in a mouse model. The rapid accumulation and activation of Vγ4+ γδ T cells in the early stage of infection triggered the IL-17A-mediated immune response. Int ...[more]

PMID: 38034361

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Project description:BackgroundStudies have revealed important roles for IL-17A in the development of acute lung injury (ALI) following sepsis. However, the mechanism underlying the regulation of lung IL-17A remains to be fully addressed. Recent studies suggested the effect of neuromedin U (NMU) on immune cell activation and the role of group 2 innate lymphoid cells (ILC2s) in the modulation of IL-17A production. We aimed to gain in-depth insight into the mechanism underlying sepsis-induced lung IL-17A production, particularly, the role of NMU in mediating neuronal regulation of ILC2s and IL-17A-producing γδ T cells activation in sepsis.MethodsWild type mice were subjected to cecal ligation and puncture (CLP) to induce sepsis with or without intraperitoneal injection of NMU. The levels of ILC2s, γδ T cells, IL-17A, NMU and NMU receptor 1 (NMUR1) in the lung were then measured. In order to determine the role of NMU signaling in ILC2 activation and the role of ILC2-released IL-9 in ILC2-γδ T cell interaction, ILC2s were sorted, and the genes of nmur1 and il9 in the ILC2s were knocked down using CRISPR/Cas9. The genetically manipulated ILC2s were then co-cultured with lung γδ T cells, and the levels of IL-17A from co-culture systems were measured.ResultsIn septic mice, the levels of NMU, IL-17A, ILC2s, and IL-17A-producing γδ T cells in the lung are significantly increased, and the expression of NMUR1 in ILC2s is increased as well. Exogenous NMU further augments these increases. The main source of IL-17A in response to CLP is γδ T cells, and lung nmur1 is specifically expressed in ILC2s. In vitro co-culture of ILC2s and γδ T cells leads to increased number of γδ T cells and higher production of IL-17A from γδ T cells, and these alterations are further augmented by septic treatment and exogenous NMU. Genetic knockdown of nmur1 or il9 in ILC2s attenuated the upregulation of γδ T cells and IL-17A production.ConclusionIn sepsis, NMU acting through NMUR1 in lung ILC2s initiates the ILC2 activation, which, in turn, promote IL-17A-producing γδ T cell expansion and secretion of IL-17A. ILC2-derived IL-9 plays an important role in mediating γδ T cell expansion and IL-17A production. This study explores a new mechanism underlying neuronal regulation of innate immunity in sepsis.

Dataset Information

Mammary γδ T cells promote IL-17A-mediated immunity against Staphylococcus aureus-induced mastitis in a microbiota-dependent manner.

Publications

Mammary γδ T cells promote IL-17A-mediated immunity against <i>Staphylococcus aureus</i>-induced mastitis in a microbiota-dependent manner.

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