The Rho GTPase signaling pathway modulates Moraxella catarrhalis invasion into human respiratory epithelial cells by

Ruirui Ma1,2, Guixue Cheng3, Yun Wu2

  • 1Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, China.

PubMed

Insights

Moraxella catarrhalis invasion, a key driver of COPD exacerbations, relies on Rho GTPase regulators. CDC42 and Rac1 are crucial for bacterial entry by controlling actin polymerization and macropinosome formation.

Area of Science:

  • Microbiology
  • Cell Biology
  • Immunology

Background:

  • Moraxella catarrhalis invasion of respiratory cells drives COPD exacerbations.
  • Actin cytoskeleton dynamics are crucial for M. catarrhalis entry, but upstream regulators are unclear.

Purpose of the Study:

  • To identify and validate Rho GTPase regulators involved in M. catarrhalis invasion.
  • To elucidate the molecular mechanisms of M. catarrhalis-induced actin polymerization and host cell entry.

Main Methods:

  • Invasion assays and Transmission Electron Microscopy (TEM) in A549 cells.
  • Utilized wild-type and knockout cell lines for CDC42, Rac1, ArpC2, and ArpC4.
  • Western blot and immunofluorescence to analyze actin dynamics.

Main Results:

  • Rho GTPase signaling regulates M. catarrhalis load by controlling macropinosome volume.
  • CDC42 and Rac1 are essential for actin polymerization and bacterial internalization.
  • ArpC4 influences actin remodeling, ArpC2 is not involved in invasion or actin dynamics.

Conclusions:

  • Rho GTPase signaling pathways are critical for M. catarrhalis invasion by modulating actin polymerization.
  • Findings provide a basis for targeting innate immunity against M. catarrhalis-induced AECOPD.

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