Type II interferon gamma is detrimental to the host in Streptococcus suis infections caused by an epidemic strain (164.6)

Abstract

Abstract S. suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. Therefore, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray, qPCR, and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with strain SC84 > P1/7 > 89-1591. Interestingly, IFNγ was expressed at much higher levels only in mice infected with strain SC84, which could potentially explain some of the STSLS symptoms. IFNγ-KO mice infected with epidemic SC84 strain showed significantly better survival than WT mice while no difference was observed in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFNγ in S. suis infections and might explain in part the increased virulence of the epidemic SC84 strain responsible for the outbreak in China.