The role of nucleotide-binding oligomerization domain 1 during cytokine production by macrophages in response to Mycobacterium tuberculosis infection

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• 作者：Jun-Young Lee^a ; Eun-Ha Hwang^b ; Dong-Jae Kim^b ; Sang-Muk Oh^b ; Kyung-Bok Lee^b ; Sung Jae Shin^c ; ^{sjshin@yuhs.ac" class="auth_mail" title="E-mail the corresponding author} ; Jong-Hwan Park^a ; ^{jonpark@jnu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BMDMs ; bone marrow-derived macrophages ; CARDs ; caspase recruitment domains ; LRRs ; leucine-rich repeats ; Nod1 ; nucleotide-binding oligomerization domain 1 ; PRR ; spattern recognition receptors
• 刊名：Immunobiology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：221
• 期：1
• 页码：70-75
• 全文大小：814 K

文摘

Tuberculosis due to Mycobacterium tuberculosis infection is a leading cause of death worldwide. Recognition of this pathogen is crucial for the activation of innate and adaptive immune responses. Nucleotide-binding oligomerization domain (Nod)1 and Nod2 are cytoplasmic receptors that can detect unique muropeptides of bacterial peptidoglycan. Nod2 is critical for the initiation of the host immune response against M. tuberculosis infection, however the role of Nod1 remains largely unknown. We investigated the role of Nod1 with respect to cytokine production by bone marrow-derived macrophages (BMDMs) in response to M. tuberculosis infection. Production of proinflammatory cytokines, such as IL-6, TNF-α, and IL-1β were induced in BMDMs; cytokine levels were not affected by a deficiency in Nod1. Activation of NF-κB and MAPKs was also comparable between wild-type and Nod1-deficient BMDMs. Levels of IL-6 and IL-1β were reduced in Nod1/Nod2 double-deficient BMDMs to a greater extent than in Nod2-deficient cells. Furthermore, when signaling of Toll-like receptors (TLRs) was inhibited by lipopolysaccharide pre-treatment, cytokine production was diminished in Nod1-deficient BMDMs. Our results indicate that Nod1 cooperates with Nod2 or TLRs to produce cytokines in macrophages in response to M. tuberculosis infection.