Human and Mouse Macrophages Collaborate with Neutrophils To Kill Larval Strongyloides stercoralis

Abstract

bMacrophages are multifunctional cells that are active in T H 1-and T H 2-mediated responses. In this study, we demonstrate that human and mouse macrophages collaborate with neutrophils and complement to kill the parasite Strongyloides stercoralis in vitro. Infection of mice with worms resulted in the induction of alternatively activated macrophages (AAM) within the peritoneal cavity. These cells killed the worms in vivo and collaborated with neutrophils and complement during the in vitro killing process. AAM generated in vitro killed larvae more rapidly than naive macrophages, which killed larvae after a longer time period. In contrast, classically activated macrophages were unable to kill larvae either in vitro or in vivo. This study adds macrophages to the armamentarium of immune components that function in elimination of parasitic helminths and demonstrate a novel function by which AAM control large extracellular parasites.

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

“…Similar findings were presented for Nippostronglyus brasiliensis-infected mice, and suppression of this neutrophil response resulted in reduced mobilization of macrophages capable of killing the parasite and alternatively activated macrophages (AAMs) [7]. In accordance with this, human and mouse neutrophils have been shown to collaborate with macrophages to kill S. steroralis larvae in vitro [8]. Finally, in the reciprocal direction of communication, the chitinase-like protein Ym1, that characterizes the murine AAM, has been shown to recruit neutrophils that contributed to the control of N. brasiliensis [9].…”

IL-17 and neutrophils: unexpected players in the type 2 immune response

“…More recently, neutrophils and macrophages have been shown to collaborate in the immobilization and killing of larval stages of the parasitic nematode Strongyloides stercoralis [36 ]. This joint venture between neutrophils and macrophages is complement dependent [36 ] and can also involve neutrophil extracellular traps (NETs) [37]. The requirement for complement is interesting in light of evidence that Mw(IL-4) at that site of nematode infection make abundant C3 [38].…”

“…In L. sigmodontis infection, blockade of the type 2 cytokine IL-5 prevented neutrophil accumulation, nodule formation and led to parasite survival [34]. More recently, neutrophils and macrophages have been shown to collaborate in the immobilization and killing of larval stages of the parasitic nematode Strongyloides stercoralis [36 ]. This joint venture between neutrophils and macrophages is complement dependent [36 ] and can also involve neutrophil extracellular traps (NETs) [37].…”

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

“…We and others have demonstrated an important role for Arginase-1-expressing MF and Abs in limiting the in vivo motility of larvae of the intestinal nematode Heligmosomoides polygyrus bakeri, a natural parasite of mice (14,19). Following infection with Strongyloides ratti, serum-activated MF collaborate with neutrophils not only to immobilize, but also to kill larvae in a complement-dependent manner (20). Thus, multiple Ab isotypes (IgE, IgG, or IgM) can activate MF and granulocytes to trap or kill helminth larvae through FcRg-chain signaling or complement activation in vivo (16,18,19,21).…”