Delayed development of the protective IL-17A response following a Giardia muris infection in neonatal mice

Abstract

Giardia is an intestinal protozoan parasite that has the ability to infect a wide range of hosts, which can result in the clinical condition ‘giardiasis’. Over the years, experimental research has shown the crucial involvement of IL-17A to steer the protective immune response against Giardia . The development of the protective response, as reflected by a significant drop in cyst secretion, typically takes around 3 to 4 weeks. However, early-life infections often have a more chronic character lasting for several weeks or months. Therefore, the aim of the current study was to investigate the dynamics of a Giardia muris infection and the subsequent host immune response in neonatal mice infected 4 days after birth. The outcome of the study showed that a G . muris infection in pre-weaned mice failed to trigger a protective IL-17A response, which could explain the prolonged course of infection in comparison to older mice. Only after weaning, a protective intestinal immune response started to develop, characterized by an upregulation of IL-17A and Mbl2 and the secretion of parasite-specific IgA.

The immunomodulatory activity of secnidazole–nitazoxanide in a murine cryptosporidiosis model

“…IL-17 triggers the production of antimicrobial peptides and complement factors, and regulates the secretion of parasite-specific immunoglobulin A (IgA) in the intestine. All these components function together in parasite clearance in the intestine [75]. In the present work a significant elevation of IL-17 level was associated with C. parvum infection in both immunocompetent and immunosuppressed compared to normal control.…”

RORγt+ Treg to Th17 ratios correlate with susceptibility to Giardia infection

“…Singer & Nash showed that C57BL/6 mice provided by two vendors (later shown to differ in SFB colonization 44 ), differed in susceptibility to Giardia infection 46 . More recently, Paerewijck and colleagues demonstrated that neonate mice infected with G. muris displayed delayed IL-17A responses and parasite control 47 . As SFB colonization and the accumulation of intestinal Th17 cells typically occurs in mice at the time of weaning 48 , the delayed control of G. muris seen after neonatal infection suggests that Th17 responses triggered by these and other microbes later in life provide an environment equipped for the partial control of Giardia infections.…”

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

“…These observations are in support of the hypothesis that SFB may contribute at least in part to the characteristic adaptive immune response observed during Giardia infection. Interestingly, neonatal mice infected with Giardia muris fail to develop a protective IL-17A response and show delayed parasite clearance compared to adult mice ( Paerewijck et al, 2019 ). IL-17A responses and IgA production were only evident after weaning ( Paerewijck et al, 2019 ).…”

“…Interestingly, neonatal mice infected with Giardia muris fail to develop a protective IL-17A response and show delayed parasite clearance compared to adult mice ( Paerewijck et al, 2019 ). IL-17A responses and IgA production were only evident after weaning ( Paerewijck et al, 2019 ). Colonization of the GI tract by SFB occurs in rat and mouse hosts at the onset of the weaning process, and thus SFB populations are low in neonates, which may contribute to their inability to mount IL-17 responses and their poor resistance to Giardia infection ( Koopman et al, 1987 ; Ericsson et al, 2014 ).…”