INTERCONNECTION · Inter-tissue communication during nematode infections: role of dermal γδ17 T cells

Inter-tissue communication during nematode infections: role of dermal γδ17 T cells

The immune system is constantly exposed to invading microorganisms. In order to promote pathogen killing without causing excessive self-damage, immune cells have to carefully choose how to respond to a given threat and generate a balanced response. Nevertheless, how this decision is made is still not fully understood. Moreover, during infection pathogens often travel through different organs, requiring local immune cells to establish an inter-tissue communication network, ensuring a concerted action throughout the body. This process, however, remains largely unexplored. In general, this knowledge gap can be attributed to the lack of suitable experimental models to address this question. Experimental infection with the parasite Nippostrongylus brasiliensis provides a great tool to overcome this problem. Infective larvae actively penetrate the skin, and then migrate through the lungs before establishing themselves in the gut. Later on, parasite elimination depends on cross-regulation of distinct and seemingly exclusive arms of the immune system. Of note, to date, little is known about the impact of the early immune responses starting in the skin in the regulation of the anti-parasitic responses taking place at later stages in the lungs and gut. In fact, the current knowledge on the skin phase of N. brasiliensis infection is fragmented and superficial, making it difficult to assess the extension of these initial immune events to an organismal level. Therefore, in this project, we employed state-of-the-art technologies to examine at an unprecedented depth the early events taking place in the skin of N. brasiliensis-infected mice. Moreover, by using different routes of infection and genetically-modified mouse models we set to investigate the cellular mechanisms underlying skin to lung communication during parasitic infections. The data generated in this project added to the field of parasitology research by generating knowledge transposable to various microorganisms, including human-threatening pathogens. Furthermore, preliminary results generated in the present project support the idea that the skin - lung axis can be extrapolated to other inflammatory conditions starting in the skin, such as allergies, by inducing similar immune mechanisms as the ones elicited during parasite infections. Overall, completion of INTERCONNECTION greatly advanced our basic knowledge of the immune events happening early in the skin during parasite infections, and their consequence in distal organs; these results might also serve as the basis for understanding complex processes in human health as the development of allergies.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз