Streptococcus uberis ST439 and ST475 induce differential inflammatory responses in a mouse intramammary infection model

• In vivo mouse model depicts real picture of host response to endemic S. uberis (n = 2).
• Comprehensive analyses showed 24 h PI as critical point to decide fate of infection.
• SU1 evoked immune response favoring its persistence in the host environment.
• SU2 elevated gene expression indicating pathogen clearance or immune surveillance.
• S. uberis manipulated immune response in strain specific manner influencing mastitis severity.

Streptococcus uberis causing mastitis is a growing challenge to the dairy industry. Molecular, epidemiological and population structure studies have revealed clonal diversity among the infecting strains. In this study, mouse intramammary infection model was used to uncover the host immune response to two epidemiologically important live strains of S. uberis (SU1and SU2) obtained from subclinical case of mastitis possessing specific and unique multi locus sequence types (ST), pulsed field gel electrophoresis (PFGE) pulsotypes and virulence profiles. Temporal (2 h, 4 h, 8 h, 12 h, 24 h and 48 h) expression of key inflammatory mediators (IL2, IL4, IL6, IL12, TNFα, IFNγ, GMCSF, TLR2, TLR4, TLR9, TLR11, TLR12, CD14, IL1β, RANTES, Lactoferrin, and CXCl1) by reverse transcription and probe-based quantitative real-time PCR showed relative mRNA levels higher (p < 0.05) in response to SU2 compared with SU1 with 24 h PI serving as a critical point for the deviating behavior (SU1 versus SU2). Further employing the predicted biological processes under the influence of this pool of tested genes, the delineation of gene regulatory networks suggested SU1− favoring its persistence in the host environment; in contrast, SU2− which elevated gene expression indicating towards pathogen clearance or immune surveillance. This study suggested how these unique strains could manipulate the host immune response to influence the severity of mastitis; our results expand the available information on host pathogen interaction and provide a firm foundation needing further investigations to gain control over this pathogen.