IL-4Rα Expression by Bone Marrow-Derived Cells Is Necessary and Sufficient for Host Protection against Acute Schistosomiasis

Herbert, De’Broski R.; Orekov, Tatyana; Perkins, Charles; Rothenberg, Marc E.; Finkelman, Fred D.

doi:10.4049/jimmunol.180.7.4948

Cited by 34 publications

(55 citation statements)

References 41 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phenotypic analysis of these cells after primary and secondary infections with S. stercoralis revealed increased expression of Relm-␣ by macrophages, a phenotype associated with AAM. Polarization of AAM in the peritoneal cavities of infected mice was dependent on IL-4 and IL-4R␣, consistent with the importance of IL-4/IL-13 signaling for the development of AAM observed during other parasite infections (39)(40)(41)(42). The presence of AAM in the peritoneal cavity following a subcutaneous injection reflects a systemic immune response likely induced by the highly motile larvae of S. stercoralis (43).…”

Section: Discussionmentioning

confidence: 52%

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

et al. 2013

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 52%

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

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Our data show that TLR2 Ϫ/Ϫ animals have decreased concentrations of IL-4, IL-5, and IL-13. Accordingly, decreased granuloma sizes have been observed in the IL-4Ra [41,42], Stat 6 [43], and IL-5 [6] gene-deleted animals, suggesting that the TLR2-dependent cytokine production and eosinophil recruitment may participate in the tissue remodeling and damage and may contribute to the pathophysiology of chronic helminth infection. Indeed, IL-5 and IL-13 have been associated with the Figure 6.…”

Section: Discussionmentioning

confidence: 98%

Schistosomal‐Derived Lysophosphatidylcholine Are Involved in Eosinophil Activation and Recruitment through Toll‐Like Receptor–2–Dependent Mechanisms

es¹,

Almeida²,

Atella³

et al. 2010

J INFECT DIS

View full text Add to dashboard Cite

Parasite‐derived lipids may play important roles in host‐pathogen interactions and escape mechanisms. Herein, we evaluated the role of schistosomal‐derived lipids in Toll‐like receptor (TLR)-2 and eosinophil activation in Schistosoma mansoni infection. Mice lacking TLR2 exhibited reduced liver eosinophilic granuloma, compared with that of wild‐type animals, following S. mansoni infection. Decreased eosinophil accumulation and eosinophil lipid body (lipid droplet) formation, at least partially due to reduced production of eotaxin, interleukin (IL)‐5, and IL‐13 in S. mansoni-infected TLR2-/- mice, compared with the corresponding production in wild‐type mice, was noted. Although no differences were observed in survival rates during the acute schistosomal infection (up to 50 days), increased survival of TLR2-/- mice, compared with survival of wild‐type mice, was observed during the chronic phase of infection. Schistosomal lipid extract– and schistosomal‐derived lysophosphatidylcholine (lyso‐PC)-stimulated macrophages in vitro induced TLR2‐dependent NF‐kB activation and cytokine production. Furthermore, in vivo schistosomal lyso‐PC administration induced eosinophil recruitment and cytokine production, in a mechanism largely dependent on TLR2. Taken together, our results suggest that schistosomal‐derived lyso‐PC may participate in cytokine production and eosinophil activation through a TLR2‐dependent pathway in S. mansoni infection. Moreover, our results suggest that TLR2‐dependent inflammatory reaction, cytokine production, and eosinophil recruitment and activation may contribute to the pathogenesis and lethality in the chronic phase of infection.

show abstract

“…These data indicated that IL-4/IL-13-induced differentiation of so-called alternatively activated macrophages (AAMs) was critical for the prevention of lethal infection (18). Interestingly, granuloma formation and protection against fatal infection are not directly linked because IL-4Ra on nonhematopoietic cells was demonstrated to be critical for granuloma formation but not for survival (19).…”

mentioning

confidence: 95%

T Cell–Derived IL-4/IL-13 Protects Mice against Fatal Schistosoma mansoni Infection Independently of Basophils

Schwartz

Oeser

Costa

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Schistosomiasis is a severe and chronic disease caused by the parasitic trematode Schistosoma mansoni after deposition of eggs in the liver and intestines. The immune response to S. mansoni eggs is characterized by increased Th2 cells, eosinophilia, and high serum IgE levels. Granulomas are formed around the eggs to protect the organs against tissue damage caused by toxic products that are secreted from the eggs. Egg-derived components have further been shown to activate the IgE-mediated release of IL-4 and IL-13 from basophils, suggesting that basophils could be involved in protection against a fatal course of infection. Using T cell–specific IL-4/IL-13–deficient mice and basophil-deficient Mcpt8Cre mice, we determined the contribution of Th2 cells and basophils for protective immunity against S. mansoni egg–induced pathology during the patent stage of infection. Our results demonstrate that T cell–derived IL-4/IL-13 was essential for granuloma formation, IgE production, basophilia, differentiation of alternatively activated macrophages, and protection against fatal infection. Although basophils were recruited into liver granulomas, they appeared to be dispensable as a source of IL-4/IL-13 both for differentiation of Th2 cells and for prevention of weight loss and mortality.

show abstract

IL-4Rα Expression by Bone Marrow-Derived Cells Is Necessary and Sufficient for Host Protection against Acute Schistosomiasis

Cited by 34 publications

References 41 publications

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

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

Schistosomal‐Derived Lysophosphatidylcholine Are Involved in Eosinophil Activation and Recruitment through Toll‐Like Receptor–2–Dependent Mechanisms

T Cell–Derived IL-4/IL-13 Protects Mice against Fatal Schistosoma mansoni Infection Independently of Basophils

Contact Info

Product

Resources

About