Table 1.
Introducing variation to the laboratory mouse during helminth infections.
Variable | Observation | References |
---|---|---|
Diet | Protein deprivation enhances susceptibility to T. muris and H. polygyrus accompanied by a reduced Type 2 immune response, in one study strain-dependent | [88,127,128] |
Zinc deficient mice suffer prolonged infections with gut nematode infections and depressed Type 2 immune responses | [89,129,130] | |
A high fat diet leads to increased resistance to T. muris infection and reduced Type 1 responses | [90] | |
Fermentable dietary fibre prevents expulsion of T. muris and heightens the Type 1 response | [91] | |
During protein deprivation, co-infection affected parasite survival and fitness via host immunity | [131] | |
Age | 18−28 months old mice are less able to clear gut nematode infections and have reduced Type 2 immune responses compared to 3 month old mice | [28,132] |
Sex | Female mice are more resistant to T. muris infection associated with elevated Type 2 cytokines | [26] |
BALB/c female mice are more susceptible to L. sigmodontis infection | [133] | |
Genetics | Inbred strains of mice differ in their ability to expel gut nematode infections | [27,134,135,136] |
Resistance to helminth infection is associated with genes within the Major Histocompatibility complex | ||
Microbiome | Helminths can upregulate microbiota-derived short chain fatty acids correlating with reduced Type 2 immune responses and increase regulation | [137] |
N. brasiliensis infection reduced segmented filamentous bacteria, reducing Th17 responses via a Type 2 mechanism | [138] | |
During a high fat diet, H. polygyrus induces gut microbiota changes via a Type 2 immune response, affecting obesity | [139] | |
H. polygryus ameliorates viral lung pathology via a microbiome dependent upregulation in Type 1 interferons | [140] | |
Multiple helminth species enrich the bacterial species Lactobacillaceae with varied outcomes on worm persistence according to the helminth species | [65,66,67,68,69,70,141] | |
Genetic and sex differences impact on how the gut microbiota responds to helminth infection | [142] | |
Infection history | Single high dose infection of between 100−400 T. muris eggs results in a dominant Type 2 immune response and worm expulsion in most mouse strains | [135] |
Low dose infection (<50 eggs) results in a Type 1 immune response and susceptibility to T. muris infection | [143] | |
Repeated low dose (“trickle”) infections enables a build-up of Type 2 immunity and ultimately worm expulsion; though outcome is influenced by genetic background | [44,143] | |
Strain-dependent, trickle infections with H. polygyrus result in a declining worm burden after several weeks | [144,145] | |
Helminth co-infections shapes immune response to future infectious challenges | [146,147,148] |
Underlined further variables altered beyond the main variable denoted on the left-hand side.