AUTHOR=Ling Zhiting , Zhao Dan , Xie Xinyu , Yao Hao , Wang Yuting , Kong Suwei , Chen Xiang , Pan Zhiming , Jiao Xin’an , Yin Yuelan 

TITLE=inlF Enhances Listeria monocytogenes Early-Stage Infection by Inhibiting the Inflammatory Response

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.748461

DOI=10.3389/fcimb.2021.748461

ISSN=2235-2988

ABSTRACT=The internalin family proteins carrying the leucine repeat region (LRRs) play diverse roles in Listeria monocytogenes infection and pathogenesis. One member of internalin family Internalin F was identified for more than 20 years, whereas its role in mediating Lm anti-inflammatory response remains unknown. Serovar 4b Lm strains are associated with the majority of listeriosis outbreaks, while the function of inlF encoded InlF protein of serovar 4b strains is poorly understood. Here, we mainly focus on the role of inlF in 4b Lm modulating inflammatory response and pathogenesis. Strikingly, inlF was highly expressed at the transcriptional level during infecting five non-phagocytic cell types, but it wasn’t involved in adhering and invading of them. However, inlF contributed to Lm adhesion and invasion to macrophages, and dramatically suppressed the expression of pro-inflammatory cytokine IL-1β and TNF-α. Similar to the results in vitro, inlF significantly inhibited the secretion of IL-1β and IL-6 in the serum of mice, as well as the expression of TNF-α and IL-6 in the liver. More importantly, InF contributed to Lm colonize in the small intestine and liver during early stage of infection via intragastric administration, inducing severe inflammatory injury and histopathology changes in the late stage. As far as we know that this is the first report of verification that inlF medicates Lm to inhibit the pro-inflammatory response and contribute to the colonization and survival in mice during early stage of infection. Our research helps to provide a reasonable explanation for the high pathogenicity of serovar 4b strains and contributes new insights to the pathogenesis and immune evasion of Lm.