title: Snapshot of spatio-temporal cytokine responses to single and co-infections with helminths and bacteria.
abstract: Cytokines play a key role in maintaining communication between organs and in so doing modulate the interaction between concurrent infections. The extent of these effects depends on the properties of the organ infected and the intensity and type of infections. To determine systemic bystander effects among organs, IFN-γ, IL-4 and IL-10 gene expression was quantified at 7 days post-challenge in directly infected and uninfected organs during single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminths Graphidium strigosum and Trichostrongylus retortaeformis. Results showed that cytokine expression in a specific organ was influenced by the type of infection occurring in another organ, and this bystander effect was more apparent in some organs than others. Within the same organ the relative cytokine expression was consistent across infections, although some cytokines were more affected by bystander effects than others. For the infected gastrointestinal tract, a stronger cytokine response was observed in the tissue that harbored the majority of helminths (i.e. duodenum and fundus). Overall, co-infections altered the intensity but to a lesser extent the relative cytokine profile against the focal infection, indicating clear bystander effects and low organ compartmentalization. However, organs appear to actively modulate cytokine expression to avoid potential immuno-pathological consequences.
authors.affiliation: Center for Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA 16802, USA ; Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Ashutosh K
authors.initials: AK
authors.lastname: Pathak
authors.affiliation: Center for Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Biarnes
authors.affiliation: Division of Animal Production and Public Health, Veterinary School, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Murphy
authors.affiliation: Center for Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA 16802, USA ; Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Isabella M
authors.initials: IM
authors.lastname: Cattadori
keywords: AR-1, autoregressive function of order 1; B, B. bronchiseptica single infection; BG, B. bronchiseptica+G. strigosum dual-infection; BT, B. bronchiseptica+T. retortaeformis dual-infection; BTG, B. bronchiseptica+T. retortaeformis+G. strigosum triple infection; Bordetella bronchiseptica; Bystander effects; Co-infections; Cytokine gene expression; DPI, days post-infection; GLM, generalized linear models; Graphidium strigosum; IFN-γ, Interferon-gamma; IL-10, Interleukin-10; IL-4, Interleukin-4; LME-REML, linear mixed effect models with restricted maximum likelihood; SI, small intestine; T, T. retortaeformis single infection; TG, T. retortaeformis+G. strigosum dual helminth co-infection; Trichostrongylus retortaeformis