Annexin A1 Attenuates Neutrophil Migration and IL-6 Expression through Fpr2 in a Mouse Model of Streptococcus suis-Induced Meningitis.

Abstract

Streptococcus suis serotype 2 is a crucial pathogenic cause of bacterial meningitis, a life-threatening disease with neurological sequelae and high rates of mortality. Inflammation triggered by S. suis infection must be precisely regulated to prevent further tissue damage. As a glucocorticoid anti-inflammatory mediator, annexin A1 (AnxA1) mainly acts through formyl peptide receptor 2 (Fpr2) to alleviate inflammation in the peripheral system. In this study, we evaluated the roles of AnxA1 and Fpr2 in a mouse model of S. suis meningitis created via intracisternal infection in Fpr2-deficient (Fpr2-/-) and wild-type (WT) mice. We revealed that Fpr2-/- mice were highly susceptible to S. suis meningitis, displaying increased inflammatory cytokine levels, bacterial dissemination, and neutrophil migration compared with WT mice. Additionally, AnxA1 exerted anti-inflammatory effects through Fpr2, such as attenuation of leukocyte infiltration, inflammatory mediator production, and astrocyte or microglial activation in the brain. Importantly, we found that the antimigratory function of AnxA1 decreases neutrophil adherence to the endothelium through Fpr2. Finally, an in vitro study revealed that AnxA1 potentially suppresses interleukin-6 (IL-6) expression through the Fpr2/p38/COX-2 pathway. These data demonstrated that Fpr2 is an anti-inflammatory receptor that regulates neutrophil migration in mice with S. suis meningitis and identified AnxA1 as a potential therapeutic option.

• Authors: Chengpei Ni, Song Gao, Yuling Zheng, Peng Liu, Yajie Zhai, Wenhua Huang, Hua Jiang, Qingyu Lv, Decong Kong, Yongqiang Jiang
• Journal: Infection and immunity (Infect Immun) Vol. 89 Issue 3 (02 16 2021) ISSN: 1098-5522 [Electronic] United States
• PMID: 33318141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Ni et al.

Chemical References

• Annexin A1
• Interleukin-6
• Receptors, Formyl Peptide
• formyl peptide receptor 2, mouse

Topics

• Animals
• Annexin A1 (metabolism)
• Cell Movement (drug effects)
• Disease Models, Animal
• Inflammation (metabolism)
• Interleukin-6 (genetics, metabolism)
• Male
• Meningitis (genetics, metabolism, pathology)
• Mice
• Neutrophils (metabolism)
• Receptors, Formyl Peptide (metabolism)
• Streptococcus suis (genetics, pathogenicity)