Interleukin-17A Contributes to Bacterial Clearance in a Mouse Model of Streptococcal Toxic Shock-Like Syndrome

Abstract

Streptococcus suis (S. suis), an emerging zoonotic pathogen, can cause streptococcal toxic shock-like syndrome (STSLS) in humans with high mortality. STSLS is characterized by high bacterial burden, an inflammatory cytokine storm, multi-organ dysfunction, and ultimately acute host death. Although it has been found that a significantly high level of IL-17A was induced in an NLRP3-dependent manner during STSLS development, the role of IL-17A on S. suis STSLS remains to be elucidated. In this study, we found that the epidemic strain SC 19 caused a significantly higher level of IL-17A than the non-epidemic strain P1/7. In addition, higher bacterial burden was observed from SC 19-infected il17a–/– mice than il17a+/+ mice, although acute death, tissue injury and inflammatory cytokines storm were observed in both types of mice. Furthermore, compared with il17a+/+ mice, the level of neutrophils recruitment was lower in il17a–/– mice, and the levels of induced antimicrobial proteins, such as CRAMP, S100A8 and lipocalin-2, were also decreased in il17a–/– mice. In conclusion, this study demonstrated that IL-17A does not contribute to the severe inflammation, although it may play a minor role for bacterial clearance by inducing antimicrobial proteins and promoting neutrophil recruitment during STSLS.

Neutrophils in Streptococcus suis Infection: From Host Defense to Pathology

“…This suggests that important mechanisms regulate neutrophil mobilization during the infection in pigs, but they remain to be elucidated. In mouse models, studies reported neutrophil recruitment in the blood [143,144] and in the peritonea after S. suis intraperitoneal infection [69,143]. Interestingly, several studies suggested that the more neutrophil numbers increased, the less bacteria were recovered in the blood [143,144], while others showed that neutrophil mobilization positively correlates with bacteremia levels [140,142].…”

“…In mouse models, studies reported neutrophil recruitment in the blood [143,144] and in the peritonea after S. suis intraperitoneal infection [69,143]. Interestingly, several studies suggested that the more neutrophil numbers increased, the less bacteria were recovered in the blood [143,144], while others showed that neutrophil mobilization positively correlates with bacteremia levels [140,142]. This suggests that an early mobilization of neutrophils allows S. suis clearance but if the infection gets the upper hand, neutrophils are recruited proportionally to bacteremia.…”

“…Several chemokines potentially attract neutrophils during an infection and S. suis infection induces the production of many of them, such as CXCL1 (KC), CXCL2 (MIP-2), CCL2 (MCP-1), CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES) [7,77,85,86,133,145]. In vivo, neutrophil mobilization positively correlated with cytokine/chemokine levels in mouse and porcine models [77,140,145], but only one study established a causality between a cytokine and neutrophil mobilization [144]. Indeed, IL-17A caused neutrophil recruitment in infected mice, despite a minor role in overall S. suis-induced inflammation [144].…”

“…In vivo, neutrophil mobilization positively correlated with cytokine/chemokine levels in mouse and porcine models [77,140,145], but only one study established a causality between a cytokine and neutrophil mobilization [144]. Indeed, IL-17A caused neutrophil recruitment in infected mice, despite a minor role in overall S. suis-induced inflammation [144].…”