Respiratory nematodiasis (Nematoda, Metastrongyloidea) is associated with marked type 2 inflammation in a marine mammal

Abstract

Type 2 inflammation, mediated by T-helper 2 (Th2) cells, promotes wound healing and clears large pathogens such as helminths. However, exacerbated type 2 inflammation can lead to tissue damage prompting a debate on the protective versus detrimental role of this response in an evolutionary context. Wild mammals with significant morbidity and mortality due to helminth infection offer a unique opportunity to understand the mechanisms and role of type 2 inflammation in a natural animal model. Here, we characterized leukocyte populations and cytokine production in the lung and lymph nodes of stranded harbour porpoises (Phocoena phocoena) infected with metastrongyle lungworms, a group of helminths that at high burdens may cause mortality in cetaceans. In the lung, the number of eosinophils, IL-4 and IL-13 producing leukocytes was higher in porpoises with mild and moderate lungworm burden compared to non-infected porpoises or individuals with severe lungworm burden. The number of T-lymphocytes was higher in porpoises with a mild burden compared to non-infected porpoises and those with moderate and severe burdens. A large proportion of these T-lymphocytes produced IL-13. The number of CD21⁺ leukocytes was higher in all lungworm infected porpoises compared to non-infected individuals, regardless of lungworm burden, while the production of IFNγ was minimal in lung or lymph nodes with the lungworm burden or infection status having no effect. Harbour porpoises with mild to moderate metastrongyle burdens recruit large numbers of Th2 committed inflammatory cells in the lung. The milder inflammation in animals with severe, potentially fatal parasite burdens, suggests that exposure to large numbers of nematodes damps down type 2 inflammation or that individuals with a milder type 2 inflammation fail to control the worm burden. This reinforces the notion that the type 2 inflammation is critical for the survival of mammals exposed to common helminth infections.