Interactions of Streptococcus suis with primary porcine respiratory cells co-infected with Bordetella bronchiseptica

• Applicant: Professor Dr. Peter Valentin-Weigand
• Subject Area: Veterinary Medical Science ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2015 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280771934

It is generally accepted that viral and bacterial co-infections in the respiratory tract predispose pigs for infections by Streptococcus suis. Most likely, the predisposing effects are due to impairment of mucociliary clearance and barrier functions as well as modulation of immune responses, which enhances adherence and invasion of S. suis. However, the processes and mechanisms of S. suis interactions with co-infected respiratory cells have not been clarified in much detail. Our previous results revealed that swine influenza virus (SIV) promotes S. suis interactions with porcine respiratory cells in a two-step process. Firstly, streptococcal adherence and colonization is facilitated by binding of its capsular polysaccharide sialic-acid residues to hemagglutinin expressed on SIV-infected cells. Secondly, S. suis invades into deeper cell layers by exploiting SIV-induced ciliostasis and impairment of the mucociliary barrier thickness. The latter process is crucial for the pathogenicity of S. suis since it is required for its invasion into the blood stream and dissemination of the pathogen.In the proposed follow-up project we will focus on the effects of mucosal damage induced by co-infecting pathogens on S. suis interactions with the porcine respiratory cell barrier. We assume that (the extent of) mucosal damage determines the outcome of S. suis infection. We will use the same primary cell models as in the previous project. However, as co-infecting pathogen we will switch from SIV to Bordetella bronchiseptica. B. bronchiseptica is known to co-infect piglets with S. suis (both contribute to the porcine respiratory disease complex). Furthermore, experimental infection showed that B. bronchiseptica predisposes piglets for subsequent intranasal infection with S. suis. Finally, our preliminary studies revealed that B. bronchiseptica induces mucosal damage, ranging from ciliostasis to shedding of ciliated cells, which enhanced adherence, invasion and cytotoxicity S. suis. Thus, our main objectives are (i) to characterize effects of (mild and severe) mucosal damage induced by co-infecting B. bronchiseptica on adherence and invasion of S. suis, (ii) to identify the role of the S. suis toxin suilysin in these interactions, and (iii) to analyse the response of B. bronchiseptica-infected porcine respiratory cells to S. suis. As gain of knowledge, we expect more insights into the complex pathogen-host interactions during the initial stages of S. suis infection and, in general, during bacterial-bacterial co-infections of the porcine respiratory tract. In addition, our analyses of host cell responses will help to identify modulations of mucosal immune responses by co-infections.

• DFG Programme: Research Grants