Collectively, this implies that in addition to shaping the local cytokine signature, specific organ–pathogen

interactions can modulate the immune profile of distal organs that may or may not be infected. Immune cells synthesizing cytokine mRNA but not protein against the intestinal helminth Heligmosomoides polygrus or the lung-resident Trichostatin A cost Influenza A virus have been found in uninfected and seemingly unrelated non-lymphoid organs (i.e. lungs, peritoneal cavity and liver), indicating the potential bystander impacts of localized infections but also stronger connectivity among some tissues compared to others [11] and [12]. Understanding the complexities of cytokine expression and their bystander stimuli during co-infections requires the quantification of these molecules against the constituent pathogens at the local site of infection and how they differ from single infected hosts. Here, we performed single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminths Graphidium strigosum and Trichostrongylus retortaeformis, pathogens that colonize distinct organs and thus prevent any confounding effect caused by their direct interaction [13] and [14]. These infections are commonly found co-inhabiting the European rabbit (Oryctolagus cuniculus) with animals getting initially exposed around 1–2 months of age based

on the pathogen [13] and [14]. Our approach was to perform infections with all the possible combinations Fludarabine manufacturer of these three pathogens and take a snap-shot of cytokine gene expression at one sampling point [7 days post-infection (DPI)] across infected (lungs, stomach and small intestine) and uninfected organs (spleen, mesenteric lymph node and when available, uninfected small intestine and stomach) to identify changes Methamphetamine in cytokine expression across different organs and type of infections. We focused on three cytokines widely identified to be instrumental in bacteria–helminth infections: IFN-γ, IL-4 and IL-10 [15] and [16]. B. bronchiseptica is a gram-negative bacterium that colonizes the respiratory tract of a wide range of mammalian hosts via oral–nasal infection [17]. We recently

showed that rabbits single infected with this bacterium mounted IFN-γ mediated antibody and neutrophil responses that led to phagocytosis and bacterial clearance from the lungs, whereas IL-10 acted antagonistically by delaying clearance [18] and [19]. This pattern was consistent in single and co-infections with T. retortaeformis, with no apparent delay in the dynamics of infection induced by the helminth [19]. In the nasal cavity however, colonies persisted with high intensities throughout the trial in both single and co-infected hosts [18] and [19], in line with mouse models [20] and [21]. G. strigosum and T. retortaeformis are extracellular gastrointestinal helminths with direct life-cycle and infections that occur by ingestion of free living third stage larvae (L3). T.