NAD(P)H Fluorescence Lifetime Imaging of Live Intestinal Nematodes Reveals Metabolic Crosstalk Between Parasite and Host

Abstract

Infections with intestinal nematodes have an ambivalent impact: they represent a burden for human health and animal husbandry, but, at the same time, may ameliorate auto-immune diseases due to the immunomodulatory effect of the parasites. Thus, it is key to understand how intestinal nematodes arrive and persist in their luminal niche and interact with the host over long periods of time. The basic mechanism ruling over parasite and host cellular and tissue functions, the metabolism, was largely neglected in the study of intestinal nematode infections. Here we use NADH (nicotinamide adenine dinucleotide) and NADPH (nicotinamide adenine dinucleotide phosphate) fluorescence lifetime imaging of explanted murine duodenum infected with the natural nematode Heligmosomoides polygyrus and define the link between general metabolic and specific enzymatic activity in parasite and host tissue, during acute infection. In both healthy and infected host intestine, energy is effectively produced, mainly via oxidative phosphorylation. In contrast, the nematodes shift their energy production from balanced fast anaerobic glycolysis and effective oxidative phosphorylation, towards mainly anaerobic glycolysis, back to oxidative phosphorylation during the different life cycle phases in the submucosa versus the intestinal lumen. Additionally, we found an increased NADPH oxidase (NOX) enzymes-dependent oxidative burst in infected intestinal host tissue as compared to healthy tissue, which was mirrored by a similar defense reaction in the parasites. We expect that, the here presented application of in vivo NAD(P)H-FLIM constitutes a unique tool to study metabolic host-parasite crosstalk, in various parasitic intestinal infections.