Concurrent Ascaris infection modulates host immunity resulting in impaired control of Salmonella infection in pigs
Ankur Midha,
Larissa Oser,
Josephine Schlosser-Brandenburg,
Alexandra Laubschat,
Robert M. Mugo,
Zaneta D. Musimbi,
Philipp Höfler,
Arkadi Kundik,
Rima Hayani,
Joshua Adjah,
Saskia Groenhagen,
Malte Tieke,
Luis E. Elizalde-Velázquez,
Anja A. Kühl,
Robert Klopfleisch,
Karsten Tedin,
Sebastian Rausch,
Susanne Hartmann
Affiliations
Ankur Midha
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Larissa Oser
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Josephine Schlosser-Brandenburg
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Alexandra Laubschat
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Robert M. Mugo
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Zaneta D. Musimbi
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Philipp Höfler
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Arkadi Kundik
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Rima Hayani
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Joshua Adjah
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Saskia Groenhagen
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Malte Tieke
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Luis E. Elizalde-Velázquez
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Anja A. Kühl
Charité Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, iPATH.Berlin, Core unit of Charité, Campus Benjamin Franklin, Berlin, Germany
Robert Klopfleisch
Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany
Karsten Tedin
Department of Veterinary Medicine, Institute of Microbiology and Epizootics, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Sebastian Rausch
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
Susanne Hartmann
Department of Veterinary Medicine, Institute of Immunology, Centre for Infection Medicine, Freie Universität Berlin, Berlin, Germany
ABSTRACT Ascaris is one of the most widespread helminth infections, leading to chronic morbidity in humans and considerable economic losses in pig farming. In addition, pigs are an important reservoir for the zoonotic salmonellosis, where pigs can serve as asymptomatic carriers. Here, we investigated the impact of an ongoing Ascaris infection on the immune response to Salmonella in pigs. We observed higher bacterial burdens in experimentally coinfected pigs compared to pigs infected with Salmonella alone. The impaired control of Salmonella in the coinfected pigs was associated with repressed interferon gamma responses in the small intestine and with the alternative activation of gut macrophages evident in elevated CD206 expression. Ascaris single and coinfection were associated with a rise of CD4-CD8α+FoxP3+ Treg in the lymph nodes draining the small intestine and liver. In addition, macrophages from coinfected pigs showed enhanced susceptibility to Salmonella infection in vitro and the Salmonella-induced monocytosis and tumor necrosis factor alpha production by myeloid cells was repressed in pigs coinfected with Ascaris. Hence, our data indicate that acute Ascaris infection modulates different immune effector functions with important consequences for the control of tissue-invasive coinfecting pathogens.IMPORTANCEIn experimentally infected pigs, we show that an ongoing infection with the parasitic worm Ascaris suum modulates host immunity, and coinfected pigs have higher Salmonella burdens compared to pigs infected with Salmonella alone. Both infections are widespread in pig production and the prevalence of Salmonella is high in endemic regions of human Ascariasis, indicating that this is a clinically meaningful coinfection. We observed the type 2/regulatory immune response to be induced during an Ascaris infection correlates with increased susceptibility of pigs to the concurrent bacterial infection.
