1. Academic Validation
  2. High-glucose conditions attenuate the response of macrophages to Legionella pneumophila infection by inhibiting NOD1 and MAPK signaling

High-glucose conditions attenuate the response of macrophages to Legionella pneumophila infection by inhibiting NOD1 and MAPK signaling

  • Int Immunopharmacol. 2024 Jun 15:134:112254. doi: 10.1016/j.intimp.2024.112254.
Yuting Zhang 1 Sicong Liang 1 Ze Deng 1 Zirui Zhao 1 Xu Han 2
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Liaoning Province, Shenyang 110001, PR China.
  • 2 Department of Emergency, Shengjing Hospital of China Medical University, Liaoning Province, Shenyang 110001, PR China. Electronic address: hanxu19881207@126.com.
Abstract

Background: Patients with diabetes are particularly susceptible to Legionella pneumophila (LP) Infection, but the exact pathogenesis of LP Infection in diabetic patients is still not fully understood. Herein, we investigated the effect of diabetes on immune function during LP Infection in vitro and in vivo.

Methods: The time course of LP Infection in macrophages under normal and high-glucose (HG) conditions was examined in vitro. Western blot was used to determine nucleotide-binding oligomerization domain 1 (NOD1), kinase 1/2 (ERK1/2), mitogen-activated protein kinase p38 (MAPK p38), and c-Jun N-terminal kinases (JNK). Enzyme-linked immunosorbent assay (ELISA) was used to assess the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Cell Counting Kit-8 (CCK8) assay assessed U937 cell viability after treating cells with different concentrations of high sugar medium and ML130 (NOD1 Inhibitor). For the in vivo study, normal and streptozocin-induced diabetic guinea pigs were infected with LP for 6, 24, and 72 h, after which NOD1, MAPK-related signals, TNF-α, and IL-6 expression in lung tissues were assessed using immunohistochemistry, western blot, and RT-PCR.

Results: HG attenuated the upregulation of NOD1 expression and reduced TNF-α and IL-6 secretion caused by LP compared with LP-infected cells exposed to normal glucose levels (all p < 0.05). In diabetic guinea pigs, HG inhibited the upregulation of NOD1 expression in lung tissues and the activation of p38, ERK1/2, and cJNK caused by LP Infection compared to control pigs (all p < 0.05).

Conclusion: HG attenuates the response of macrophages to LP Infection by inhibiting NOD1 upregulation and the activation of MAPK signaling.

Keywords

Diabetes; Glucose; Legionella pneumophila; MAPK; Macrophage; NOD1.

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