Live Brugia malayi Microfilariae Inhibit Transendothelial Migration of Neutrophils and Monocytes

Abstract

Lymphatic filariasis is a major tropical disease caused by the parasite Brugia malayi. Microfilariae (Mf) circulate in the peripheral blood for 2–3 hours in synchronisation with maximal feeding of the mosquito vector. When absent from the peripheral blood, Mf sequester in the capillaries of the lungs. Mf are therefore in close contact with vascular endothelial cells (EC) and may induce EC immune function and/or wound repair mechanisms such as angiogenesis. In this study, Mf were co-cultured with human umbilical vein EC (HUVEC) or human lung microvascular EC (HLMVEC) and the transendothelial migration of leukocyte subsets was analysed. In addition, the protein and/or mRNA expression of chemokine, cytokine and angiogenic mediators in endothelial cells in the presence of live microfilariae were measured by a combination of cDNA arrays, protein arrays, ELISA and fluorescence antibody tests.Surprisingly, our findings indicate that Mf presence partially blocked transendothelial migration of monocytes and neutrophils, but not lymphocytes. However, Mf exposure did not result in altered vascular EC expression of key mediators of the tethering stage of extravasation, such as ICAM-1, VCAM-1 and various chemokines. To further analyse the immunological function of vascular EC in the presence of Mf, we measured the mRNA and/or protein expression of a number of pro-inflammatory mediators. We found that expression levels of the mediators tested were predominantly unaltered upon B. malayi Mf exposure. In addition, a comparison of angiogenic mediators induced by intact Mf and Wolbachia-depleted Mf revealed that even intact Mf induce the expression of remarkably few angiogenic mediators in vascular EC. Our study suggests that live microfilariae are remarkably inert in their induction and/or activation of vascular cells in their immediate local environment. Overall, this work presents important insights into the immunological function of the vascular endothelium during an infection with B. malayi.

Brugia malayi Microfilariae Induce a Regulatory Monocyte/Macrophage Phenotype That Suppresses Innate and Adaptive Immune Responses

“…Asymptomatically infected patients are the only filarial-exposed group in which monocytes in the blood come into contact with live microfilariae; thus monocytes may be influenced at this early time point in their differentiation to contribute to immune regulation and therefore the development of asymptomatic infection. Indeed it has been shown that B. malayi microfilariae act on monocytes from filaria non-endemic normal donors to reduce transendothelial migration [45] . To this end, we established that monocytes and macrophages from non-endemic normal donors stimulated with B. malayi Mf lysate in vitro develop a specific phenotype upon activation, and that these cells may influence either the adaptive or innate immune response, respectively.…”

Cell Type-Specific Immunomodulation Induced by Helminthes: Effect on Metainflammation, Insulin Resistance and Type-2 Diabetes

“…68 Bm-SNP-2, a serpin secreted by the helminth Brugia malayi, was found to neutralize at least two neutophil enzymes, namely, Cathepsin G and elastase. 69 Furthermore, live B. malayi was found to inhibit transendothelial migration of neutrophils 70 via Th2 cytokines IL-4 and IL-13. 71 Because accumulation of activated neutophils in the VAT is a major event associated with IR, inhibition of neutrophil migration/activation could be a major factor contributing to helminth-induced inhibition of IR.…”

A Trypsin-Sensitive Proteoglycan from the Tapeworm <b><i>Hymenolepis diminuta</i></b> Inhibits Murine Neutrophil Chemotaxis in vitro by Suppressing p38 MAP Kinase Activation

“…Schroeder et al reported that live microfilariae of Brugia malayi blocked transendothelial migration of neutrophils but did not determine if this was via the release of a molecule from the nematode [31]. We add 2 speculative points when interpreting our data.…”