Faculty Collaboration Database

The TRPM2 Ion Channel Regulates Inflammatory Functions of Neutrophils During Listeria monocytogenes Infection. Front Immunol 2020;11:97

Date

03/03/2020

Pubmed ID

32117251

Pubmed Central ID

PMC7010865

DOI

10.3389/fimmu.2020.00097

Scopus ID

2-s2.0-85079677223 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

During infection, phagocytic cells pursue homeostasis in the host via multiple mechanisms that control microbial invasion. Neutrophils respond to infection by exerting a variety of cellular processes, including chemotaxis, activation, phagocytosis, degranulation and the generation of reactive oxygen species (ROS). Calcium (Ca²⁺) signaling and the activation of specific Ca²⁺ channels are required for most antimicrobial effector functions of neutrophils. The transient receptor potential melastatin-2 (TRPM2) cation channel has been proposed to play important roles in modulating Ca²⁺ mobilization and oxidative stress in neutrophils. In the present study, we use a mouse model of Listeria monocytogenes infection to define the role of TRPM2 in the regulation of neutrophils' functions during infection. We show that the susceptibility of Trpm2^-/- mice to L. monocytogenes infection is characterized by increased migration rates of neutrophils and monocytes to the liver and spleen in the first 24 h. During the acute phase of L. monocytogenes infection, Trpm2^-/- mice developed septic shock, characterized by increased serum levels of TNF-α, IL-6, and IL-10. Furthermore, in vivo depletion of neutrophils demonstrated a critical role of these immune cells in regulating acute inflammation in Trpm2^-/- infected mice. Gene expression and inflammatory cytokine analyses of infected tissues further confirmed the hyperinflammatory profile of Trpm2^-/- neutrophils. Finally, the increased inflammatory properties of Trpm2^-/- neutrophils correlated with the dysregulated cytoplasmic concentration of Ca²⁺ and potentiated membrane depolarization, in response to L. monocytogenes. In conclusion, our findings suggest that the TRPM2 channel plays critical functional roles in regulating the inflammatory properties of neutrophils and preventing tissue damage during Listeria infection.

Author List

Robledo-Avila FH, Ruiz-Rosado JD, Brockman KL, Partida-Sánchez S

Author

Kenneth Brockman PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Calcium Signaling
Cell Death
Cytokines
Disease Models, Animal
Gene Expression
Inflammation
Listeria monocytogenes
Listeriosis
Membrane Potentials
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils
Oxidative Stress
TRPM Cation Channels