Platelet-activating factor receptor deficiency delays elimination of adult worms but reduces fecundity in Strongyloides venezuelensis-infected mice.
We describe the parasitological kinetics and histopathological and immunological alterations in platelet-activating factor receptor-deficient (PAFR(-/-)) and wild-type mice after a single Strongyloides venezuelensis infection (subcutaneous inoculation of 500 L3 larvae). There was no difference in the numbers of worms that reached and became established in the small intestines of PAFR(-/-) and wild-type mice. However, at 12 days after infection, significantly more worms were recovered from PAFR(-/-) mice. Although PAFR(-/-) infected mice showed a delay in elimination of adult worms, worms established in the small intestine of these mice produced a significantly lower number of eggs due to a reduction in worm fecundity. There were also significant reductions in the number of circulating and tissue eosinophils and tumor necrosis factor levels in the small intestines of PAFR(-/-) mice infected for 7 days compared to the number and level in wild-type mice. Histological analysis confirmed the reduced inflammatory process and revealed that the PAFR(-/-) mice had a smaller number of goblet cells. The concentrations of the type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-10 were lower in small intestine homogenates and in supernatants of antigen-stimulated lymphocytes from spleens or mesenteric lymph nodes of PAFR(-/-) mice than in the corresponding preparations from wild-type mice. Thus, in S. venezuelensis-infected PAFR(-/-) mice, decreased intestinal inflammation is associated with enhanced worm survival but decreased fecundity. We suggest that although a Th2-predominant inflammatory response decreases worm survival, the worm may use factors produced during this response to facilitate egg output and reproduction. PAFR-mediated responses appear to modulate these host-derived signals that are important for worm fecundity.
Negrão-Corrêa
Deborah
D
Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. denegrao@icb.ufmg.br
Souza
Danielle G
DG
Pinho
Vanessa
V
Barsante
Michele M
MM
Souza
Adriano L S
AL
Teixeira
Mauro M
MM
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007421:Intestine, Small / Q000469:parasitology / Q000473:pathology; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D010270:Parasite Egg Count; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000502:physiology*; D013321:Strongyloides / Q000302:isolation & purification*; D013322:Strongyloidiasis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor