ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
This article is part of the Research TopicMetabolic Pathways in Host-Pathogen Interactions: From Immune Response to Therapeutic ImplicationsView all articles
The Rho GTPase signaling pathway modulates Moraxella catarrhalis invasion into human respiratory epithelial cells by regulating actin polymerization
Provisionally accepted
- 1Peking Union Medical College Hospital (CAMS), Beijing, China
- 2Shengjing Hospital of China Medical University, Shenyang, China
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Moraxella catarrhalis invasion of host respiratory epithelial cells is a critical mechanism driving acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Although previous studies have extensively demonstrated that dynamic changes in the actin cytoskeleton are central to the invasion of host cells by Moraxella catarrhalis, the detailed mechanisms underlying the specific upstream signaling pathways and key regulators driving this process remain incompletely understood. Our study identifies and validates the essential roles of key Rho GTPase regulators (CDC42, Rac1,ArpC2, ArpC4) in actin polymerization during M. catarrhalis infection, thereby elucidating a more comprehensive and specific molecular mechanism. Invasion assays and TEM showed that the Rho GTPase signaling pathway modulates M. catarrhalis bacterial load in A549 cells by regulating macropinosome volume. Further experiments used M. catarrhalis strains 73-OR and ATCC 25238 to invade wild-type A549 cells, CDC42-/- A549 cells, Rac1-/- A549 cells, ArpC2-/- A549 cells and ArpC4-/- A549 cells respectively. Invasion assays and TEM to quantify internalized bacteria, macropinosome volume changes, and bacterial distribution; Western blot analyses and cellular immunofluorescence to measure F-actin/G-actin ratios and microfilament fluorescence intensity. These results indicate that Rho GTPase signaling pathway modulates M.catarrhalis invasion by regulating actin polymerization dynamics. Specifically, CDC42 and Rac1 are essential for actin polymerization and bacterial internalization. ArpC4 contributes to actin remodeling without influencing invasion, while ArpC2 is uninvolved in both processes. These findings provide a theoretical basis for targeting innate immunity to prevent and treat M. catarrhalis-induced AECOPD.
Keywords: f-actin, G-actin, invasion, Moraxella catarrhalis, Rho GTPase
Received: 23 Oct 2025; Accepted: 28 Jan 2026.
Copyright: © 2026 Ma, Cheng, Wu, Chen, Lu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yali Liu
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