Regulatory functional role of NLRP3 inflammasome during Mycoplasma hyopneumoniae infection in swine

Our study uncovered the crucial regulatory role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in managing the invasion of respiratory mycoplasma in swine. The findings of our research suggest that the levels of NLRP3 expression can serve as a reliable diagnostic indicator for identifying Mycoplasma hyopneumoniae infection. Furthermore, inhibiting NLRP3 could offer therapeutic advantages in treating NLRP3-related disorders, such as porcine enzootic pneumonia. Mycoplasma hyopneumoniae causes enzootic pneumonia, a highly contagious respiratory disease in swine that causes significant economic losses worldwide. It is unknown whether the nucleotide oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome regulates the immune response in swine during M. hyopneumoniae infection. The current study utilized an in vivo swine model of M. hyopneumoniae infection to investigate the regulatory functional role of the NLRP3 inflammasome during M. hyopneumoniae infection. Notable histopathological alterations were observed in M. hyopneumoniae-infected swine tissues, which were associated with an inflammatory response and disease progression. Swine M. hyopneumoniae infection was associated with an increase in the expression of the NLRP3 inflammasome, which stimulated pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin 18, and interleukin 1 beta (IL-1 & beta;). The impact of the NLRP3 inhibitor, MCC950 on NLRP3 and pro-inflammatory cytokines in M. hyopneumoniae-infected swine was examined to investigate the relationship between the NLRP3 inflammasome and M. hyopneumoniae infection. Taken together, our findings provide strong evidence that the NLRP3 inflammasome plays a critical regulatory functional role in M. hyopneumoniae infection in swine. Lay Summary Our study highlights the importance of controlling the innate immune defense against respiratory mycoplasma invasion to suppress mycoplasma growth and minimize lung tissue damage. Using an in vivo swine model, we investigated the regulatory functional role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome during acute Mycoplasma hyopneumoniae infection. Furthermore, we also found that NLRP3 expression levels have the potential to serve as a novel diagnostic marker for detecting M. hyopneumoniae infection in the respiratory tract of pigs. The NLRP3 inhibitor, MCC950, was used to investigate how NLRP3 inhibition affects the expression of inflammatory cytokines, and it was found that the NLRP3 inhibitor significantly reduced the mRNA and protein expression of NLRP3, indicating its specific targeting of the NLRP3 inflammasome during M. hyopneumoniae infection in swine. The findings suggest that MCC950 is a promising therapeutic option for treating NLRP3-related disorders, including porcine enzootic pneumonia.