Phosphorylcholine‐bearing antigens in filarial nematode parasites: analysis of somatic extracts, in‐vitro secretions and infection sera from <i>Brugia malayi</i> and <i>B. pahangi</i>

Maizels, Rick M.; Burke, J. C.; Denham, D. A.

doi:10.1111/j.1365-3024.1987.tb00488.x

Cited by 93 publications

(40 citation statements)

References 39 publications

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“…In this regard, one nonprotein epitope that has repeatedly been shown to be immunodominant in filarial infection is phosphorylcholine (33)(34)(35)(36)(37)(38)(39). In preliminary experiments (data not shown), we have found that a mAb of the IgM isotype (PC 140) (40) directed against phosphorylcholine does not facilitate the adherence of activated peritoneal cells to larvae.…”

Section: Discussionmentioning

confidence: 92%

Critical Role for IgM in Host Protection in Experimental Filarial Infection

Rajan

Ramalingam

Rajan

2005

The Journal of Immunology

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We have previously shown that B cells (in particular B1 cells) are important in host protection against brugian infections in a murine i.p. model. In this study, we show that mice deficient in circulating IgM (secIgM−/−), but otherwise normal in their humoral responses, manifest a significant impairment in worm elimination, suggesting that one critical B cell function is the production of Ag-specific IgM. Efficient elimination of larvae is IgM dependent for both primary and challenge infections. The ability to eliminate worms is restored in secIgM−/− mice by administering sera from primed mice. We corroborated these in vivo studies with in vitro observations which show that IgM is the only isotype that reacts strongly with the surface of Brugia L3. Furthermore, activated peritoneal exudate cells adhere to L3 only in the presence of filaria-specific sera or IgM purified from them. This attachment is not reduced by heat inactivation of the serum, suggesting complement independent activity. Peritoneal exudate cells from primed mice, especially activated macrophages, carry high levels of IgM on their surfaces. Our observations suggest that an IgM-mediated reaction initiates the formation of host-protective granulomas.

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Section: Discussionmentioning

confidence: 92%

Critical Role for IgM in Host Protection in Experimental Filarial Infection

Rajan

Ramalingam

Rajan

2005

The Journal of Immunology

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“…Many of the immunodominant epitopes of these type 2-inducing antigens have been shown to be glycans displaying very unique structures (10,32,34). We had previously observed that mice immunized with an extract of the human nematode parasite Brugia malayi from which N-linked glycans had been enzymatically removed failed to produce antigen-specific IL-4 (unpublished observation).…”

mentioning

confidence: 99%

Both Free-Living and Parasitic Nematodes Induce a Characteristic Th2 Response That Is Dependent on the Presence of Intact Glycans

et al. 2004

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Infection with parasitic nematodes is characterized by the induction of a profound type 2 immune response. We have studied the role of glycans in the induction of the skewed type 2 response by antigens of the parasitic nematode Brugia malayi as well as the free-living nematode Caenorhabditis elegans. Lymph node cells from BALB/c mice immunized with soluble extracts of the two nematodes showed distinct antigen-specific proliferation and cytokine production; however, both nematodes induced antigen-specific interleukin 4 (IL-4) production, demonstrating that the induction of a biased type 2 response is not unique to parasitic nematodes. Sodium periodate-treated soluble extracts of both nematodes consistently induced significantly less IL-4 production than the respective mock-treated extracts, indicating that glycans play a critical role in the induction of the Th2 immune response by these nematodes. The glycan-dependent induction of the Th2-potentiating cytokine IL-4 occurs by 72 h postinoculation. Our data suggest that glycan determinants common to nematodes act as ligands, displaying distinct molecular patterns that trigger the immune system to launch a biased Th2 immune response upon exposure to these organisms or their products. Further, the similarity of our findings to those for Schistosoma mansoni egg antigen is striking considering the enormous phylogenetic distance between nematodes and trematodes. These data thus have important implications for how the mammalian host responds to widely divergent metazoan invaders and suggest that the powerful C. elegans model system can be used to address these questions.

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“…The possibility that monoclonal antibodies directed against filarial antigen may react with Fasciola antigen was examined by ELISA Two antibodies CA,,, and C$,, both directed against the PC epitope of filarial antigens Phosphocholine is a ubiquitous epitope detected in many parasites including the protozoans (Lal and Ottesen, 1989), cestodes (Fletcher d al., 1980) and nematodes (Lal et al, 1987, Maizels et al, 1987. The present study demonstrates that the trematode F. gtganticxl also bears PC epitopes.…”

Section: M4bs To Fdarial Antigen Cross-react With Fasciola Antigenmentioning

confidence: 57%

“…Development of antigen capture assays for human fhriasis have led to identification of phosphocholine (PC) as an immunodominant epitope on filarial parasite (La1 et aZ;, Maizels et al, 1987 and antibodies directed against the PC can detect filarial antigens in most of the infected individuals. Subsequently, it was shown that PC epitope is not only shared among the helminth parasites, but also was present on some protozoan parasites (La1 and Ottesen, 1989).…”

Section: Introductionmentioning

confidence: 99%