CXCR1, TLR4, and CXCL8: Key Mediators of Pseudomonas aeruginosa Virulence in Wound and Burn Infections

Pseudomonas aeruginosa, an opportunistic pathogen of considerable clinical import, presents a formidable challenge to susceptible individuals, particularly within the confines of nosocomial settings. Those with compromised immune systems, indwelling medical devices such as catheters, and extensive thermal injuries are especially vulnerable to its insidious and often devastating effects. This investigation sought to elucidate the roles of Toll-like receptor 4 (TLR4), Toll-like receptor 5 (TLR5), the chemokine CXCL8, and its cognate receptor CXCR1 in the context of P. aeruginosa infection. Our findings indicate a significant involvement of TLR4 and CXCL8 in the host response to this pathogen. Notably, CXCR1 expression was observed to be downregulated both in cellular models and in whole blood samples obtained from patients afflicted with bacterial infections, specifically those caused by P. aeruginosa. Utilizing antibodies targeting these cell surface molecules, we further explored their influence on bacterial adhesion and the modulation of infection. The application of anti-CXCR1 antibodies resulted in a demonstrable increase in bacterial infection in both T24 and A549 cell lines. Conversely, the administration of anti-TLR4 antibodies exerted an inhibitory effect on P. aeruginosa infection. Anti-CXCL8 antibodies, however, did not elicit a discernible impact on bacterial infection within the initial three hours of exposure. These observations suggest a dichotomous role for these molecules in the host response to P. aeruginosa: CXCR1 appears to function as a negative regulator, while TLR4 appears to act as a positive regulator in the context of bacterial infection.

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