Effect of Nippostrongylus brasiliensis L3 ES on inflammatory mediator gene transcription in lipopolysaccharide lung inflammation

Abstract

The anti-inflammatory properties of parasitic helminths have been largely linked to their excretory-secretory (ES) products. Some studies have noted a lack of TNF-alpha production and limited recruitment of neutrophils into the lungs after Nippostrongylus brasiliensis infection. We previously reported that instillation of ES from L3 larvae of N. brasiliensis to the lungs could inhibit the recruitment of neutrophils on a background of LPS-induced inflammation. A similar reduction in neutrophil recruitment was observed in this study. This reduction was associated with the significant inhibition in gene transcription of the adhesion molecule, ICAM-1, and the chemokine, MIP-2 in bronchoalveolar lavage (BAL) cells. The LPS-stimulated gene transcription of the pro-inflammatory cytokines TNF-alpha and IL-1beta was also significantly reduced by L3 ES. Inducible nitric oxide synthase (iNOS) is normally elevated in classically activated macrophages, however, in this case gene transcription of iNOS was inhibited by L3 ES and may suggest a phenotype change to anti-inflammatory. The general inhibition of pro-inflammatory mediators observed in this study suggests that infective stage L3 larvae excrete and/or secrete inhibitory products capable of modifying the normally potent LPS inflammatory response.

Hookworm infections: Reappraising the evidence for a role of neutrophils in light of NETosis

“…brasiliensis abrogates Lipopolysaccharides (LPS)‐induced lung neutrophilia. 32 , 33 Similarly, H . polygyrus also reduces the level of neutrophil‐specific chemokines in mice in a model of contact hypersensitivity.…”

“…For example, whole ES isolated from N . brasiliensis abrogates Lipopolysaccharides (LPS)‐induced lung neutrophilia 32,33 . Similarly, H .…”

“…For example, whole ES isolated from N. brasiliensis abrogates Lipopolysaccharides (LPS)induced lung neutrophilia. 32,33 Similarly, H. polygyrus also reduces the level of neutrophil-specific chemokines in mice in a model of contact hypersensitivity. 34 While hookworm ES proteins have now been studied for several decades, only a few functions are fully characterized.…”

Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus

“…Both IL-4 and IL-13 enhance smooth muscle contractility in the small intestine [119], a mechanism that has been shown to be important for resistance to other helminth infections including Schistosoma mansoni [120], T. spiralis [121, 122], and N. brasiliensis [123]. Increased intestinal smooth muscle contractility has been shown after infection with H. polygyrus [124].…”