Effects of Pseudomonas aeruginosa and Streptococcus mitis mixed infection on TLR4-mediated immune response in acute pneumonia mouse model

Chao Song, Hongdong Li, Yunhui Zhang, Jialin Yu

Our previous research on the diversity of microbiota in the endotracheal tubes (ETTs) of neonates in the neonatal intensive care unit found that Pseudomonas aeruginosa (P. aeruginosa) and Streptococcus mitis (S. mitis) were the dominant bacteria on the ETT surface and the existence of S. mitis could promote biofilm formation and pathogenicity of P. aeruginosa. Toll-like receptor 4 (TLR4), which has been widely detected on the surface of airway epithelial cells, is the important component of the innate immune system. Therefore, we hypothesized that the co-existence of these two bacteria might impact the host immune system through TLR4 signaling. S. mitis rarely caused inflammation, whereas P. aeruginosa caused the most severe inflammation accompanied by increases in the number of inflammatory cells, interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression, and total cell counts in BALF (p < 0.05). In the PAO1 + S. mitis group, moderate inflammation, reduced IL-6 and TNF-α protein levels, and decreased total cell counts were observed. Additionally, levels of these indicators were decreased lower in TLR4-deficient mice than in wild-type mice (p < 0.05). Our results demonstrated that infection with S. mitis together with P. aeruginosa could alleviate lung inflammation in acute lung infection mouse models possibly via the TLR4 signaling pathway.