Lennart Heepmann (Hamburg / DE), Dr. Wiebke Hartmann (Hamburg / DE), Dr. rer nat Lara Linnemann (Hamburg / DE), Laura Scherer (Hamburg / DE), Prof. Dr. Minka Breloer (Hamburg / DE)
Abstract text
Introduction:
Helminths dampen their host`s immune response. Among other things, helminths induce expansion of regulatory lymphocytes and checkpoint molecules with co-inhibitory functions such as B and T lymphocyte attenuator (BTLA), a ligand of Herpes Virus Entry Mediator (HVEM). Another HVEM ligand is CD160, which is described on various T cell subsets, NK cells, innate lymphoid cells (ILCs) and mast cells.
Objective:
Aim of the study was to investigate the role of the CD160 in helminth infected mice.
Material and Methods:
I used Strongyloides ratti was used as a model for helminth infection with a tissue migration and an intestinal phase. Taking advantage of CD160-deficient (CD160-/-), we performed a tight kinetic study of S. ratti infection. Furthermore, the impact of CD160 on the innate immune response using RAG-/-mice that lack T and B lymphocytes but express CD160, and CD160-/-RAG-/- mice that additionally lack CD160 was investigated. Worm burden was analyzed at different timepoints. Flow cytometry was used to analyze which cell types express CD160 in S. ratti-infected mice. Additionally the expansion/contraction of CD160-expressing cells during S. ratti infection was investigated.
Results:
Numbers of migrating larvae in the tissues were unchanged but numbers of adult worms in the intestine day 6 p.i. were reduced in CD160-/- mice compared to wildtype mice. CD160-/-RAG-/-mice also showed reduced intestinal parasite burden day 6 p.i. Although RAG-/- mice cannot completely eject Strongyloides parasites, they control the parasite burden from initially ca 100 parasites to 2-5 parasitic adults per mouse. In RAG-/- mice with additional absence of CD160the initially lower parasite burden day 6 p.i. remained stable for almost 100 days. This was associated with impaired mast cell activation in CD160-/-RAG-/-mice.
Intestinal NK cells, ILC1, ILC2 and ILC3 express CD160 in naïve mice. During S. ratti infection sSpecifically, CD160+ ILC2 expand while CD160-deficiency interfered with ILC2 but not with NK cell expansion during infection.
Conclusion:
In combination, these results suggest that CD160-mediated signals have dual and opposing functions during intestinal helminth infection, antagonizing early innate immune responses but promoting late innate immune response.