Manipulation of the balance between Th2 and Th2/1 hybrid cells affects parasite nematode fitness in mice

Abstract

T-helper type 2 (Th2) responses are central to the control of helminth infections, but sensitive to opposing cytokine signals favoring Th1 priming. We previously reported on GATA-3 + T-bet + Th2/1 hybrid cell differentiation in helminth mono-infections, resulting in a substantial proportion of cells coproducing IFN-γ next to Th2 cytokines. Here, we demonstrate Th2/1 cells as the major source of parasite-specific IFN-γ production in acute and chronic infections with the enteric nematode Heligmosomoides polygyrus. Th2/1 cells differentiated from naive precursors and accumulated in spleen and intestine of infected mice, resulting in increased systemic and mucosal IFN-γ production. IFN-γ supplementation early during infection supported Th2/1 differentiation, associated with elevated parasite fecundity and the maintenance of high worm burdens in the chronic stage of infection, whereas mice lacking IFN-γ signals generated poor Th2/1 responses and restricted parasite fecundity more efficiently. These findings suggest that Th2/1 hybrid responses take part in immune regulation during helminth infection and restrain effective anti-helminth immunity.Keywords: hybrid r IFN-γ, nematode r Th1 r Th2Additional supporting information may be found online in the Supporting Information section at the end of the article.

Microarray Analysis of lncRNA and mRNA Reveals Enhanced Lipolysis Along With Metabolic Remodeling in Mice Infected With Larval Echinococcus granulosus

“…Parasites have developed refined machinery to evade the host's immune system by manipulating its response (Gomes et al, 2016). It is well known that T-helper type 2 (Th2) responses are central to parasitic infections, and can participate in regulation of host's immune system (Affinass et al, 2018). Th2 responses can create an anti-inflammatory immune microenvironment and improve host metabolic disorders (van der Zande et al, 2019).…”

“…Currently, obesity is a main public health concern since obese individuals are at a greater risk of developing chronic disease and often present clinical parameters of metabolic syndrome (MetS), insulin resistance, and systemic markers of chronic lowgrade inflammation (Alberti et al, 2005;Andersen et al, 2016;Affinass et al, 2018). Adipose tissue accumulation is a common clinical phenomenon in obese individuals (Gijs, 2017).…”

“…An increasing number of studies have shown that parasitic infection can regulate adipogenesis. The intestinal nematode parasite Heligmosomoides polygyrus was reported to attenuate obesity in high-fat diet-induced obese mice (Affinass et al, 2018). The infected individuals exhibited a markedly upregulated expression of uncoupling protein 1 (a key protein involved in energy expenditure) in the adipose tissue, suppression of glucose and triglyceride levels, and alteration in the expression of key genes involved in lipid metabolism (Su et al, 2018).…”

T-bet fate mapping identifies a novel ILC1-ILC2 subsetin vivo

“…This cytokine-driven phenomenon defined as plasticity has also been shown for ILC. As such, it has been observed that NKp46 + ILC3 can differentiate to ILC1 and vice versa (reviewed in Klose et al, 2020), and likewise ILC2 have shown plasticity to ILC1 and ILC3 (Bal et al, 2016, Ohne et al 2016, Lim et al, 2016, Huang et al, 2015and Zhang et al, 2018, Golebski et al, 2019. In humans and mice, IL-12 and IL-18 appear to be the most potent factors to induce T-bet and IFN-γ in ILC2 (Bal et al, 2016, Ohne et al 2016, Lim et al, 2016.…”

“…It has been shown that plasticity in T cells is not always absolute. CD4 + T cells coexpressing T-bet and RORγt or T-bet and GATA3 expression have been characterized (Jenner et al 2009, Affinass et al, 2018, Peine et al, 2013. NKp46 + ILC3 are known to express RORγt and T-bet, but it is not known whether ILC exist that co-express GATA3…”