NLRP12 Mediates Macrophage Polarization and Drives Host Defense Against Severe Klebsiella Pneumoniae Pneumonia.

BACKGROUND

Klebsiella pneumoniae (Kp) is a bacterial pathogen that results in diverse infections. NLRP12, one of the NLR family members, acts as an inflammasome in response to specific infections. Herein, the role and mechanisms of NLRP12 involving in severe Kp pneumonia were investigated.

METHODS

SD rats were infected with Kp and manipulated with shNLRP12 lentivirus, macrophage M1 polarization inhibitor (abietic acid), and autophagy activator (rapamycin). Hematoxylin and eosin (HE) staining, bacterial load in lung tissue, and ELISA were used to assess lung tissue injury and inflammation in rats. NLRP12 and autophagy proteins LC3B II/I and p62 in lung tissues were detected by immunohistochemistry and western blot. Flow cytometric analyses were followed to calculate the proportion of M1 and M2 macrophages in BALF.

RESULTS

In addition, NLRP12 was upregulated in lung tissue of rats with Kp infection-caused severe pneumonia, while NLRP12 knockdown enhanced Kp-induced M1 polarization of macrophages and exacerbated lung injury and inflammatory response. NLRP12 attenuated inflammation caused by Kp infection by reducing macrophage M1 polarization. Kp infection induced autophagy deficiency in rat lung tissues, while activation of autophagy could ameliorate Kp-induced lung injury and inflammation.

CONCLUSION

NLRP12 facilitates autophagy to affect macrophage M1 polarization and drives host defense against Kp infection.