Eimeria falciformis infection of the mouse caecum identifies opposing roles of IFNγ-regulated host pathways for the parasite development

Abstract

Intracellular parasites reprogram host functions for their survival and reproduction. The extent and relevance of parasite-mediated host responses in vivo remains poorly studied, however. We utilized Eimeria falciformis, a parasite infecting the mouse intestinal epithelium, to identify and validate host determinants of parasite infection. Most prominent mouse genes induced during the onset of asexual and sexual growth of parasite comprise interferon γ (IFNγ)-regulated factors, e.g., immunity-related GTPases (IRGA6/B6/D/M2/M3), guanylate-binding proteins (GBP2/3/5/6/8), chemokines (CxCL9-11), and several enzymes of the kynurenine pathway including indoleamine 2,3-dioxygenase 1 (IDO1). These results indicated a multifarious innate defense (tryptophan catabolism, IRG, GBP, and chemokine signaling), and a consequential adaptive immune response (chemokine-cytokine signaling and lymphocyte recruitment). The inflammation- and immunity-associated transcripts were increased during the course of infection, following influx of B cells, T cells, and macrophages to the parasitized caecum tissue. Consistently, parasite growth was enhanced in animals inhibited for CxCr3, a major receptor for CxCL9-11 present on immune cells. Interestingly, despite a prominent induction, mouse IRGB6 failed to bind and disrupt the parasitophorous vacuole, implying an immune evasion by E. falciformis. Furthermore, oocyst output was impaired in IFNγ-R(-/-) and IDO1(-/-) mice, both of which suggest a subversion of IFNγ signaling by the parasite to promote its growth.

Eimeria falciformisBayerHaberkorn1970 and novel wild derived isolates from house mice: differences in parasite lifecycle, pathogenicity and host immune reactions

“…falciformis BayerHaberkorn1970 (Haberkorn, 1970) Between the two E. falciformis isolates BayerHaberkorn1970 and Brandenburg88 we observed only slight differences in the length of the pre-patent period (time until oocyst shedding, starting at 6 vs. 7 dpi). These results are in agreement with previous reports from the same host (NMRI mice) and the BayerHaberkorn1970 isolate (Stange et al, 2012;Schmid et al, 2012Schmid et al, , 2014Ehret et al, 2017). The pre-patent period for the wild derived E. falciformis isolate (7 dpi) corresponds to that reported for the parasite isolate E. falciformis var praghensis (Mesfin et al, 1978;Kasai et al, 1991), but Mahrt and Shi (1988) and Schito et al (1996) demonstrated slightly longer pre-patent periods (7 or 8 dpi) also in other E. falciformis infections.…”

“…The output of oocysts in our study (for all isolates) was similar or only slightly lower than in previous reports (Schmid et al, 2014;Ehret et al, 2017). Our observation regarding the lifecycle progression of E. ferrisi, agree with the initial description of the life cycle in Mus musculus (Ankrom et al, 1975).…”

“…Eimeria species capable of natural infection of the house mouse (Mus musculus) have been proposed as a model for e.g. host immune response against Eimeria Schmid et al, 2014). Serial passaging of laboratory isolates of Eimeria is usually conducted by collecting oocysts at the day of peak shedding.…”

“…The isolate E. falciformis BayerHaberkorn1970 has been isolated in 1960 (Haberkorn 1970) and since has been propagated in laboratories (first at Bayer animal health, Monheim, Germany; then at the institute for molecular parasitology of the Humboldt University, Berlin, Germany). In nearly 60 years since its isolation E. falciformis BayerHaberkorn1970 has likely become the most commonly used laboratory isolate of rodent Eimeria (Mahrt and Shi 1988;Schito et al, 1996;Steinfelder et al, 2005;Pogonka et al, 2010;Stange et al, 2012;Schmid et al, 2014Schmid et al, , 2012Ehret et al, 2017).…”

Host specificity of turkey and chicken Eimeria: Controlled cross-transmission studies and a phylogenetic view

“…Such mechanism would enable continuation of the parasite development even under fully active immunity of the host. It was shown that Eimeria parasites are able to compromise signalling and modulate gene expression of the host in order to support their development (del Cacho et al, 2004;Taubert et al, 2006Taubert et al, , 2010Fetterer et al, 2007;Guo et al, 2013;Schmid et al, 2014). If such immune evasion is an important determinant of the host specificity, it would be not surprising that the pattern of host specificity is not reflected in the phylogenetic tree of Eimeria.…”