Journal
MICROBIAL PATHOGENESIS
Volume 169, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.micpath.2022.105671
Keywords
Staphylococcus aureus; TLR2; TLR4; NLRP3; Immune -driven resistance and tolerance
Categories
Funding
- National Natural Science Foundation of China [32160854, 31860722, 31860720]
- Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region [NJYT22041]
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Staphylococcus aureus infection can induce host immune responses, and TLR2, TLR4, and NLRP3 play important roles in regulating the inflammatory response. However, their roles may vary at different timepoints.
Staphylococcus aureus (S. aureus) is a gram-positive pathogen that can cause infectious diseases in mammals. S. aureus-induced host innate immune responses have a relationship with Toll-like receptor 2 (TLR2), TLR4, and Nod-like receptor pyrin domain-containing protein 3 (NLRP3). However, the detailed roles of TLR2, TLR4, and NLRP3 in regulating the host inflammatory response to S. aureus infection remain unclear. Our data indicated that the S. aureus-induced mortality was aggravated by deficiency of TLR2, TLR4, and NLRP3 in mice. In the subsequent experiment, we found that during S. aureus infection, the roles of TLR2, TLR4, and NLRP3 seemed to be different at multiple timepoints. The deficiency of TLR2, TLR4, or NLRP3 attenuated the expression of High -mobility group box protein 1 (HMGB1) and Hyaluronic acid-binding protein 2 (HABP2), which is accompanied by decreased proinflammatory cytokine (TNF-alpha), chemokine (RANTES), and anti-inflammatory cytokine (IL-10) production in lungs and serum at 3 h and 6 h post-infection. However, with S. aureus infection prolonged (24 h post-infection), the trend was diametrically opposite. The results showed that deficiency of TLR2, TLR4, or NLRP3 aggravated HABP2 and HMGB1 expression, which is accompanied by enhanced proinflammatory cyto-kine (TNF-alpha), chemokine (RANTES), and anti-inflammatory cytokine (IL-10) production in lungs and serum. These results were consistent with the data observed in S. aureus-infected bone marrow-derived macrophages (BMDMs). All these results suggested that during S. aureus infection, TLR2, TLR4, and NLRP3 has time-dependent effect in regulating the balance between immune-driven resistance and tolerance.
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