Calreticulin from the intestinal nematode Heligmosomoides polygyrus is a Th2-skewing protein and interacts with murine scavenger receptor-A.
Helminth infections are commonly associated with a Th2 immune response, yet only a few parasite molecules involved in triggering such immune responses have been identified. Here, we describe the Th2-skewing property of calreticulin of Heligmosomoides polygyrus (HpCRT). HpCRT is a secreted protein most abundantly expressed by tissue invasive larvae (L4). Native HpCRT purified from adult worm extract (nHpCRT) stimulated robust IL-4 release from CD4(+) T cells of H. polygyrus infected mice. Interestingly, CD4(+) T cells also produced significant amounts of IL-10 while IFN-gamma was not detectable. Likewise, immunization with recombinant HpCRT (rHpCRT) without extrinsic adjuvant led predominantly to a specific IL-4 production implying the innate ability of HpCRT to drive Th2 responses. The triggering of a Th2-skewed immune response to rHpCRT is corroborated by the induction of HpCRT-specific IgG1 and IgE antibodies. Furthermore, rHpCRT bound to scavenger receptor type A (SR-A) on dendritic cells, and interaction of HpCRT with SR-A led to internalization of HpCRT that could be partially blocked by competition with SR-A ligands as well as with an anti-SR-A monoclonal antibody. Hence, our data imply that nematode calreticulin interacts with a mammalian scavenger receptor and at the same time induces a Th2 response.
Rzepecka
Justyna
J
Department of Molecular Parasitology, Humboldt-University, Philippstr. 13, 10115 Berlin, Germany.
Rausch
Sebastian
S
Klotz
Christian
C
Schnöller
Corinna
C
Kornprobst
Tina
T
Hagen
Jana
J
Ignatius
Ralf
R
Lucius
Richard
R
Hartmann
Susanne
S
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000276:immunology; D037282:Calreticulin / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D015801:Helminth Proteins / Q000276:immunology / Q000378:metabolism*; D006373:Helminthiasis / Q000276:immunology*; D007114:Immunization; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009351:Nematospiroides dubius / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D037282:Calreticulin; D015801:Helminth Proteins; D008024:Ligands; D011994:Recombinant Proteins; D051117:Scavenger Receptors, Class A; D016753:Interleukin-10; D015847:Interleukin-4