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.

Excretory/secretory proteins inhibit host immune responses by downregulating the TLR4/NF-κB/MAPKs signaling pathway: A possible mechanism of immune evasion in parasitic nematode Haemonchus contortus

“…During helminth infection, TLR4 activation induced eosinophil infiltration and increased secretion of mucosal secretory immunoglobulin A (SIgA) antibodies in the infected area, facilitating worm expulsion ( 76 ). NF-κB is one of the core downstream signals of TLRs/MyD88, and its activation promotes the release of inflammatory mediators (TNF-α, IL-6, IL-1β) ( 77 ).…”

Eosinophils in Colorectal Cancer: Emerging Insights into Anti-Tumoral Mechanisms and Clinical Implications

“…Eosinophils also contribute to the homeostasis of the gastrointestinal barrier. Upon activation of TLR2 and TLR4, eosinophils release a mixture of cytokines, including IL-1β and keratinocyte growth factor [ 11 , 22 , 29 , 30 , 31 ]. These changes in the microenvironment promote IgA switching in germinal centers and epithelial integrity [ 11 , 22 , 29 , 30 ].…”

“…Upon activation of TLR2 and TLR4, eosinophils release a mixture of cytokines, including IL-1β and keratinocyte growth factor [ 11 , 22 , 29 , 30 , 31 ]. These changes in the microenvironment promote IgA switching in germinal centers and epithelial integrity [ 11 , 22 , 29 , 30 ]. Moreover, eosinophils can also promote T-independent IgA switching, but the exact mechanism is not fully understood [ 28 ].…”

Diet‐microbiota crosstalk and immunity to helminth infection

“…To this date, the results have been somewhat conflicting—mice administered the probiotic candidate Lacticaseibacillus casei were shown to be more susceptible to T. muris infection, 90 whereas mice administered Lacticaseibacillus rhamnosus (JB‐1) had enhanced immunity to the same parasite in an IL‐10‐dependent manner 91 . T. spiralis infections can be controlled through enhanced immunity brought about by treatment with heat‐killed A. muciniphila , 72 whilst Lactobacillus lactis may promote immunity to the lung stages of A. suum in mice by promoting sIgA production 92 . In porcine models of helminth infection, several studies have shown that probiotic treatment tends to diminish, rather than promote, helminth‐specific immunity.…”