Host PTX3 Protein and Bacterial Capsule Coordinately Regulate the Inflammatory Response during Streptococcus suis Infection

SIMPLE SUMMARY: Streptococcus suis serotype 2 (SS2) is a noteworthy zoonotic pathogen that has been responsible for substantial economic losses to the swine industry and a great threat to human health. In this study, the role of Pentraxin 3 (PTX3) during SS2 infection is explored to verify its potential as a new and effective biological agent that could partially resolve the problems posed by SS2. The study’s results showed that PTX3 facilitated the phagocytosis of macrophage Ana-1 against SS2 strain HA9801, and contributed to inflammatory cell recruitment and cytokine IL-6 release in the mouse air pouch; thus, it was conductive to bacterial clearance during the SS2 infection. The presence of capsular polysaccharide of SS2 (CPS2) was identified as being required for PTX3 to trigger the inflammatory activation; this coordinating modulation of the host’s innate immune response during the SS2 infection further suggested that PTX3 is a potential biological agent for the prevention and treatment of streptococcosis caused by SS2. However, the recommended dose of PTX3 must be further evaluated to avoid an excessive inflammatory response. ABSTRACT: Streptococcus suis serotype 2 (SS2) is a noteworthy zoonotic pathogen that has been responsible for large economic losses in pig production and a great threat to human health. Pentraxin 3 (PTX3) is an essential regulator of the innate immune response to bacterial pathogens; however, its role during SS2 infection is not fully understood. In this study, we found that the SS2 strain HA9801 induced a significant inflammatory response in the mouse air pouch model; this response was amplified by the treatment of exogenous PTX3 simultaneously in terms of the results of inflammatory cell recruitment and proinflammatory cytokine IL-6 production. In addition, PTX3 facilitated the phagocytosis of macrophage Ana-1 against SS2 strain HA9801. The supplementation of exogenous PTX3 significantly reduced the bacterial loads in a dose-dependent manner in lungs, livers and bloods of SS2-infected mice compared to the samples with HA9801 infection alone; this finding indicated that PTX3 may facilitate the bacterial clearance through enhancing the host inflammatory response during SS2 infection. Both PTX3 and SS2 capsular polysaccharide (CPS2) were required for the robust inflammatory response, implying that the host PTX3 protein and SS2 surface CPS2 modulate the host innate immune response in concert. All of these results suggested that PTX3 is a potential novel biological agent for the SS2 infection; however, the recommended dose of PTX3 must be evaluated strictly to avoid inducing an excessive inflammatory response that can cause serious tissue injury and animal death.