Toll-Like Receptor 4 Protects Against Clostridium perfringens Infection in Mice

Abstract

Toll-like receptor 4 (TLR4) has been reported to protect against Gram-negative bacteria by acting as a pathogen recognition receptor that senses mainly lipopolysaccharide (LPS) from Gram-negative bacteria. However, the role of TLR4 in Gram-positive bacterial infection is less well understood. Clostridium perfringens type A is a Gram-positive bacterium that causes gas gangrene characterized by severe myonecrosis. It was previously demonstrated that C. perfringens θ-toxin is a TLR4 agonist, but the role of TLR4 in C. perfringens infection is unclear. Here, TLR4-defective C3H/HeJ mice infected with C. perfringens showed a remarkable decrease in survival rate, an increase in viable bacterial counts, and accelerated destruction of myofibrils at the infection site compared with wild-type C3H/HeN mice. These results demonstrate that TLR4 plays an important role in the elimination of C. perfringens. Remarkable increases in levels of inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF), were observed in C. perfringens-infected C3H/HeN mice, whereas the increases were limited in C3H/HeJ mice. Generally, increased G-CSF accelerates granulopoiesis in the bone marrow and the spleen to exacerbate neutrophil production, resulting in elimination of bacteria. The number of neutrophils in the spleen was increased in C. perfringens-infected C3H/HeN mice compared with non-infected mice, while the increase was lower in C. perfringens-infected C3H/HeJ mice. Furthermore, DNA microarray analysis revealed that the mutation in TLR4 partially affects host gene expression during C. perfringens infection. Together, our results illustrate that TLR4 is crucial for the innate ability to eliminate C. perfringens.

A mixture of organic acids and thymol protects primary chicken intestinal epithelial cells from Clostridium perfringens infection in vitro

“… Guo et al (2015) already observed that PGN treatment did not significantly affect TLR2 expression in chicken intestinal epithelial cells. Recently, Takehara et al (2021) speculated that CPA and PFOA could activate the TLR4 on intestinal cells. This result was observed also in this study by the qPCR expression of TLR4.…”

Immunoinformatic analysis of the whole proteome for vaccine design: An application to Clostridium perfringens

“…Docking was performed against TLR1/TLR2 and TLR4/MD2, as they have been widely reported to be important in the innate defense against C. perfringens infection in chickens and mice ( 136 ), although little is known in humans. The lipopeptide and lipopolysaccharide binding sites of TLR1/TLR2 and TLR4/MD-2, respectively, have been structurally characterized ( 137 , 138 ).…”

G Protein-Coupled Receptor 120 Mediates Host Defense against Clostridium perfringens Infection through Regulating NOD-like Receptor Family Pyrin Domain-Containing 3 Inflammasome Activation

“…perfringens, TLR2 and TLR4 were implicated in sensing C. perfringens and were beneficial to the host . Previously, we also provided evidence demonstrating that mixed lineage kinase-like protein (MLKL) contributes to host protection against C.…”

“…Concerning C. perfringens, TLR2 and TLR4 were implicated in sensing C. perfringens and were beneficial to the host. 5 Previously, we also provided evidence demonstrating that mixed lineage kinaselike protein (MLKL) contributes to host protection against C. perfringens invasion via facilitating NLRP3 inflammasomeextracellular traps axis. 6 Therefore, it is not surprising that exploring the innate immunity mechanisms of host combat against C. perfringens will be conducive to the development of new strategies for the effective control of C. perfringens infection.…”