Eosinophils mediate SIgA production triggered by TLR2 and TLR4 to control Ascaris suum infection in mice

Abstract

Human ascariasis is the most prevalent but neglected tropical disease in the world, affecting approximately 450 million people. The initial phase of Ascaris infection is marked by larval migration from the host’s organs, causing mechanical injuries followed by an intense local inflammatory response, which is characterized mainly by neutrophil and eosinophil infiltration, especially in the lungs. During the pulmonary phase, the lesions induced by larval migration and excessive immune responses contribute to tissue remodeling marked by fibrosis and lung dysfunction. In this study, we investigated the relationship between SIgA levels and eosinophils. We found that TLR2 and TLR4 signaling induces eosinophils and promotes SIgA production during Ascaris suum infection. Therefore, control of parasite burden during the pulmonary phase of ascariasis involves eosinophil influx and subsequent promotion of SIgA levels. In addition, we also demonstrate that eosinophils also participate in the process of tissue remodeling after lung injury caused by larval migration, contributing to pulmonary fibrosis and dysfunction in re-infected mice. In conclusion, we postulate that eosinophils play a central role in mediating host innate and humoral immune responses by controlling parasite burden, tissue inflammation, and remodeling during Ascaris suum infection. Furthermore, we suggest that the use of probiotics can induce eosinophilia and SIgA production and contribute to controlling parasite burden and morbidity of helminthic diseases with pulmonary cycles. Ascariasis is the most prevalent but neglected tropical disease in the world, affecting more than 450 million people, mainly children. The parasites life cycle can be divided into the following two distinct phases after the initial infection: (i) the first stage called larval ascariasis involves migration of parasitic larval stages through several tissues (intestinal mucosa, blood circulation, liver, and lung/airways) and is marked by mechanical injuries, followed by an intense local inflammatory response, (ii) the second involves the establishment of adult worms in the lumen of the small intestine, causing the despoilment of nutrients and secretory/excretory parasitic products that downmodulate host immune response and characterize the chronic infection. Innate and adaptive immune responses are intrinsically connected and their cross-talk is very important for host homeostasis and is crucial in dealing with helminthiasis. In this study, we evaluated the importance of eosinophils mediating IgA production in mucosal sites, tissue inflammation, and remodeling, as well as controlling parasite burden during experimental larval ascariasis. This study provides a new perspective suggesting that stimulation by probiotics may prevent the lung pathology associated with ascariasis.