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C8 Resistance and tolerance of hybrid hosts against co-infections: the role of innate immune response and microbiome (Heitlinger)

Research Group: Department of Molecular Parasitology, Humboldt Universität zu Berlin
& Leibniz Institute for Zoo and Wildlife Research (IZW)
Address: Humboldt-Universität zu Berlin, Department of Biology, Molecular Parasitology, Philippstr. 13, House 14, 10115 Berlin; IZW, Alfred-Kowalke-Str. 17, 10315 Berlin
Supervisors: Prof. Dr. Emanuel Heitlinger
Doctoral Researcher: Totta Ehret Kasemo, Lubomír Bednář; Victor Hugo Jarquín Díaz

Project Description

State of the art:
Outbred host can be vigorous in their response against infections. Natural hybrids between the
house mouse subspecies Mus musculus domesticus and M. m. musculus show a lower
prevalence of infection with oxyurid nematodes than pure strains and their bacterial
microbiomes are perturbed. Mechanisms underlying hybrid immune vigor are not
understood, but generally, immune reactions against parasites have been shown to be
influenced by co-infections and the bacterial microbiome.

Previous own work:
Our studies in house mouse hybrid zone (HMHZ) around Berlin found lower prevalence and
intensity of Eimeria spp. in hybrids compared to more pure mice. Laboratory infections of mice
with Eimeria falciformis revealed host responses during the first days of infection. Rag-/-
mutants confirmed that partial resistance to repeated infection is independent of the adaptive
immune system. We developed techniques improving the assessment of bacterial and
eukaryotic microbiomes in house mice and other wildlife systems.

Hypotheses and work plan:
1) The innate immune system plays a key role in the immunological vigor of hybrid hosts.
2) This holds true for infections with Eimeria, helminths and for co-infections.
3) A perturbed hybrid microbiome affects not only the host but also parasites negatively.
The project investigates the house mouse and its parasites as wildlife system on the molecular
level. We can rely on an established collection of tissue and intestinal content samples of ~200
mice, spanning a continuous gradient of hybridization. We will sequence (16S and 18S)
amplicons to investigate the intestinal microbiome and to determine infection status with
Eimeria and oxyurids. For the same mice we will then sequence transcriptomes of caecum
tissue. When infections are present, this results in “dual-transciptomes” for both hosts and
parasites.
We will integrate these data using correlation networks and test the relative importance of i)
host immune response markers, ii) infection with known parasites (including co-infections) and
iii) abundance of bacterial taxa. We predict network nodes linking between (co-)infection status
and/or microbiome components to be enriched for markers of innate immune response (e.g.
cytokines). We aim to identify contrasting immunological pathways with either similar or
opposite effects on microbiome richness and parasite abundance.
We will then challenge findings from these studies using laboratory infections. We will use wild
derived pure strains of house mice and their hybrids. We will infect these with Eimeria and
oxyurid nematodes and obtain dual-transcriptomes of infected tissue and bacterial metatranscriptomes
of the intestinal content (caecum). We will again use correlated mRNA
expression and association with phenotypic outcomes of resistance and tolerance to infection
to pinpoint interacting molecular pathways in hosts, parasites and the microbiome.

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