A matter of timing: early, not chronic phase intestinal nematode infection restrains control of a concurrent enteric protozoan infection.

Infections with parasitic worms are often long lasting and associated with modulated immune responses. We analyzed the influence of the nematode Heligmosomoides polygyrus bakeri dwelling in the small intestine on concurrent protozoan infection with Eimeria falciformis residing in the cecum. To dissect the effects of a nematode infection in the early versus chronic phase, we infected animals with E. falciformis 6 or 28 days post H. p. bakeri infection. Only a concurrent early nematode infection led to an increased replication of the protozoan parasite, whereas a chronic worm infection had no influence on the control of E. falciformis. Increased protozoan replication correlated with the reduced production of IFN-γ, IL-12/23, CCL4, CXCL9 and CXCL10, reduced migration of T cells and increased expression of Foxp3 at the site of protozoan infection. This was accompanied by a stronger nematode-specific Th2 response in gut-draining LN. Protection of mice against challenge infections with the protozoan parasite was not altered. Hence, the detrimental effect of a nematode infection on the control of a concurrent protozoan infection is transient and occurs only in the narrow time window of the early phase of infection.

Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes.

Epithelial-resident T lymphocytes, such as intraepithelial lymphocytes (IELs) located at the intestinal barrier, can offer swift protection against invading pathogens. Lymphocyte activation is strictly regulated because of its potential harmful nature and metabolic cost, and most lymphocytes are maintained in a quiescent state. However, IELs are kept in a heightened state of activation resembling effector T cells but without cytokine production or clonal proliferation. We show that this controlled activation state correlates with alterations in the IEL mitochondrial membrane, especially the cardiolipin composition. Upon inflammation, the cardiolipin composition is altered to support IEL proliferation and effector function. Furthermore, we show that cardiolipin makeup can particularly restrict swift IEL proliferation and effector functions, reducing microbial containment capability. These findings uncover an alternative mechanism to control cellular activity, special to epithelial-resident T cells, and a novel role for mitochondria, maintaining cells in a metabolically poised state while enabling rapid progression to full functionality.

New insights into the excystation process and oocyst morphology of rodent Eimeria species.

In this study, the mechanism of excystation of the rodent parasites Eimeria nieschulzi, from rats, and Eimeria falciformis, from mice, was investigated. In vitro, oocysts of both species are susceptible to the protease pepsin, and sporocysts and sporozoites can be excysted in a similar way. Scanning electron microscopy (SEM) revealed a collapse of the oocysts wall at both polar ends after pepsin treatment. This occurs without any visible damage of the outer wall. Using fluorescence and transmission electron microscopy (TEM) we observed that pepsin enters sporulated oocysts at both polar ends and causes degradation of the inner oocyst wall. Using scanning electron microscopy we could identify two polar caps in both investigated rodent Eimeria species, but only one is harbouring the micropyle. Thus the polar caps are the entry site for the pepsin. Furthermore, we provide evidence that the oocyst cap and micropyle are functionally different structures. This study complements the morphological description of both Eimeria species and is of relevance for other coccidian species.