Essential role of Rnd1 in innate immunity during viral and bacterial infections.

Abstract

Intracellular and cell surface pattern-recognition receptors (PRRs) are an essential part of innate immune recognition and host defense. Here, we have compared the innate immune responses between humans and bats to identify a novel membrane-associated protein, Rnd1, which defends against viral and bacterial infection in an interferon-independent manner. Rnd1 belongs to the Rho GTPase family, but unlike other small GTPase members, it is constitutively active. We show that Rnd1 is induced by pro-inflammatory cytokines during viral and bacterial infections and provides protection against these pathogens through two distinct mechanisms. Rnd1 counteracts intracellular calcium fluctuations by inhibiting RhoA activation, thereby inhibiting virus internalisation. On the other hand, Rnd1 also facilitates pro-inflammatory cytokines IL-6 and TNF-α through Plxnb1, which are highly effective against intracellular bacterial infections. These data provide a novel Rnd1-mediated innate defense against viral and bacterial infections.

• Authors: Akhilesh Kumar, Shalabh Mishra, Ashish Kumar, Ashwin Ashok Raut, Seiichi Sato, Akinori Takaoka, Himanshu Kumar
• Journal: Cell death & disease (Cell Death Dis) Vol. 13 Issue 6 Pg. 520 (06 02 2022) ISSN: 2041-4889 [Electronic] England
• PMID: 35654795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Cytokines
• RND1 protein, human
• Receptors, Pattern Recognition
• Interferons
• rho GTP-Binding Proteins

Topics

• Bacterial Infections
• Cytokines
• Humans
• Immunity, Innate
• Interferons
• Receptors, Pattern Recognition
• rho GTP-Binding Proteins (genetics)