NLRP6 Induces Lung Injury and Inflammation Early in Brucella and Influenza Coinfection

Abstract

(1) Background: With the resurgence of brucellosis epidemics in China in recent years, the chances of a brucella coinfection with other common respiratory pathogens, such as the influenza virus, have increased dramatically. However, little is known about the pathogenicity or the mechanisms of brucella and influenza coinfections. (2) Methods: To clarify the interventions in the early stages of lung damage due to brucella and influenza coinfections, we evaluated the effect of the coinfection on disease progression and mortality using a coinfection model in WT mice and NLRP6−/− mice, and we verified the function of NLRP6 in infection and proinflammation. (3) Results: The coinfection induced significant respiratory symptoms, weight loss, and a high mortality rate in WT mice. Influenza in the coinfection group significantly increased brucella proliferation in a synergistic manner. Meanwhile, a histological examination showed severe lung tissue destruction and excessive inflammatory responses in coinfected WT animals, and the expression of NLRP6 and IL-18 was dramatically increased in the lung tissues. Furthermore, NLRP6 deletion attenuated lung injuries and inflammation, a reduced bacterial load, and decreased IL-18 protein expression. (4) Conclusions: Our findings indicated that NLRP6 plays a critical role and might be a promising potential therapeutic target for brucella–influenza coinfections.

Roles of airway and intestinal epithelia in responding to pathogens and maintaining tissue homeostasis

“…During lung infections, NLRP6 exhibits diverse effects depending on the microbe (Ghimire et al, 2018;Xu et al, 2021;Shi et al, 2022). NLRP6 plays a damaging role in the intestinal phase of Brucella infection (Rungue et al, 2021).…”