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Research

Effect of intestinal parasites on distal immune responses

Parasitic infections are still a big problem in many parts of the world, negatively affecting the health of the poorest and most vulnerable populations. On the other hand, changes in infectious exposure and microbiota over the past century, most evidently in the Western world the loss of instestinal parasites, coincide with a steady increase in immune mediated diseases. Since parasitic infections normally have co-evolved with their host and are often chronic in their nature, their presence is and has been a driving force in shaping the host immune system both at individual and population level.

Understanding the marks microorganisms leave in the host is highly relevant to understanding differentiation of T cells in tissues and the implication this has on the ability to respond to subsequent infections and vaccination or contributing to the over-reactivity seen in autoimmune diseases. It has been demonstrated that intestinal worm infection can alter immune responses to other pathogens, vaccines, autoantigens, allergens and contact sensitizers. These effects have been believed to be due to expansion of TREG and/or TH2 cells, changes in the intestinal microbiota or its metabolome, or, as we have shown, atrophy of superficial lymph nodes (Feng 2018). Yet, the full spectrum of helminth-induced effects on the immune system remains to be elucidated.

Research in my group address how parasitic infection affect formation and maintainance of immunity to co-infections (e.g. Mycobacteria, Leishmania, Influenza virus) and vaccines. We have focused on immune responses distal to the site of infection and the ability of intestinal worms to modulate barrier tissue such as the skin. We use the intestinal nematode Heligmosomoides polygurus as model to address the impact of gut infection on T cells seeding into tissues and the longlasting effects these cells have on their local environment. Specifically, we aim to defined factors that determine T cell distribution and colonization of tissue following infection and the implication this may have on tissue immunity. 

Understanding factors that influence the durability of vaccine-induced immunity and how this may differ in populations with different infectious burden is critical for making informed decisions on vaccination and boosting strategies relevant to both human and animal disease and welfare.

Development of antimicrobial resistance in parasites

Epigenetic modifications can allow fast adaptation to environmental changes (such as drugs) and may precede the mutations in development of antimicrobial resistance. This may be particularly relevant for larger parasites, like worms. In collaboration with KI colleagues ,  and , as well as two colleagues from Uppsala University Andrea Hinas and Staffan Svärd, we address drug development and epigenetic modifications in several eukaryotic parasites including worms.

Visceral Leishmaniasis

In collaboration with Banaras Hindu University, I am involved in studies of Visceral leishmaniasis in Bihar state, India, in a project aiming to understand immune responses, in particular T cells responses that determine outcome and control of Leishmania donovani parasites.