Consequences of the roundworm Ascaris suum on bacterial coinfections in pigs

• Applicant: Professorin Dr. Susanne Hartmann
• Subject Area: Veterinary Medical Science
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445163355

Infections with the roundworm Ascaris and with non-typhoid Salmonella spp. are highly prevalent in low-and-middle-income countries. Furthermore, both pathogens are extremely widespread in commercial pig farming, which poses a serious zoonotic threat to human health. However, the pig as natural host for both pathogens which similarly infect humans also offers a valuable model for studies on potential consequences of coinfections relevant to human infection research. Despite these facts, information on the outcome of Ascaris/Salmonella co-infection is scarce. In the current funding period, we addressed this gap and investigated the consequences of acute Ascaris infection for the control of a Salmonella Typhimurium (ST) challenge. Coinfection resulted in increased bacterial burden in vivo and exposure of lung macrophages to the Ascaris-induced type 2 cytokine profile resulted in impaired ST killing in vitro. Further, the phenotype and function of porcine natural killer (NK) cells was systemically altered in A. suum single and Ascaris-Salmonella coinfection, evident in reduced IFN-γ production, lower cellular degranulation capacity, and in the upregulation of inhibitory NK cell receptors. Conversely, serum profiles of Ascaris-specific IgM, IgA, IgG1/2 antibody responses were not altered in pigs exposed to the Salmonella challenge. Our aims for the prolongation period are as follows: A) to clarify if differences in the magnitude and localization of Th2 responses between acute and chronic Ascaris infection differentially affect Salmonella control by myeloid cells and if chronic ascariasis results in microbial dissemination beyond the ‘MLN firewall’. In addition, potential alterations in humoral and T cell responses to Salmonella will be determined. Part B) aims to disentangle if Ascaris larval migration dictates NK cell functional repression and recovery. We will test whether ATP - adenosine release from damaged host cells lead to the regulation of effector functions in macrophages, neutrophils and NK cells. Recovery of innate immune functions after completion of larval body migration will be surveyed in chronic Ascaris infection. The aim of part C) is to broaden the understanding of potential detriments associated with Ascaris infection on a bacterial coinfection. Salmonella will be replaced by Streptococcus suis, another highly prevalent pig pathogen with high zoonotic potential. Here, the impact of Ascaris on the invasion of S. suis across the mucosal barriers and the associated implications for mucosal immune cells and tissues in pigs will be studied in detail. Together, these investigations will be a first step towards filling the gap concerning consequences of roundworm-microbial co-infections in one of the most important livestock species worldwide.

• DFG Programme: Research Grants