title: Sensitization with anti-inflammatory BmAFI of Brugia malayi allows L3 development in the hostile peritoneal cavity of Mastomys coucha.
abstract: Filarial parasites survive by inducing tolerance in host but the antigens and mechanisms involved are not clear. Recently we found that BmAFI, a Sephadex G-200 eluted fraction of Brugia malayi adult worm extract, stimulates IL-10 release from THP-1 cells. In the present study, we determined the SDS-PAGE profile of BmAFI and infective 3rd stage larva (L3), investigated the effect of pre-sensitization of host with BmAFI on the survival and development of L3 in the non-permissive peritoneal cavity (p.c.) of the permissive host Mastomys coucha and in the p.c. of non-permissive Swiss mice, and studied immunological correlates for the observed effects. The parasite development and burden in p.c., was determined in sensitized infected M. coucha and Swiss mice and the release of TGF-β, IL-4, IL-10, IL-13, IFN-γ and NO, cellular proliferative response to Con A and BmAFI and levels of IgG subclasses and IgE were determined in sensitized infected M. coucha. Cellular proliferative response to Con A and BmAFI, mRNA expression of GATA-3, CTLA-4 and T-bet were determined in sensitized Swiss mice. In addition, the parasitological parameter was also studied in BmAFI-sensitized M. coucha exposed to the infection by standard subcutaneous (s.c.) route to assess whether sensitization enhances the intensity of infection. BmAFI-sensitization permitted survival of L3 and their development to adult stage by day 60 p.i. in the p.c. of M. coucha; in non-sensitized animals L3 could molt to L4 only and no parasite could be recovered beyond day 30 p.i. In M. coucha that received infection by s.c. route, pre-sensitization with BmAFI enhanced the microfilaraemia and adult worm recovery. In sensitized Swiss mice L3 could successfully molt to L4 in p.c. with improved recovery of parasite. BmAFI sensitization upregulated TGF-β and IL-10 release, IgG1 and IgG2b levels, GATA-3 and CTLA-4 mRNA expression, suppressed the cellular proliferative response and downregulated Con A stimulated response, IgE, IL-13, IFN-γ and NO responses. Immunoblot analysis showed that the BmAFI antiserum also strongly reacts with some L3 molecules. The results show, for the first time, that sensitization with the anti-inflammatory BmAFI which shares some of its molecules with those in L3, facilitates parasite survival in the non-permissive p.c. of the permissive host M. coucha, render a non-permissive Swiss mouse partially permissive to infection and enhances parasite load in M. coucha receiving the infection through permissive s.c. route by evoking a modified Th2 type of response and anti-inflammatory milieu. In conclusion, the findings suggest that the anti-inflammatory BmAFI fraction facilitates survival of B. malayi infection even in non-permissive environment.
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Joseph
authors.forename: S K
authors.initials: SK
authors.lastname: Verma
authors.forename: M K
authors.initials: MK
authors.lastname: Sahoo
authors.forename: S
authors.initials: S
authors.lastname: Dixit
authors.forename: A K
authors.initials: AK
authors.lastname: Verma
authors.forename: V
authors.initials: V
authors.lastname: Kushwaha
authors.forename: K
authors.initials: K
authors.lastname: Saxena
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.forename: J K
authors.initials: JK
authors.lastname: Saxena
authors.forename: P K
authors.initials: PK
authors.lastname: Murthy
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000276:immunology / Q000378:metabolism*; D017178:Brugia malayi / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005368:Filariasis / Q000276:immunology / Q000469:parasitology* / Q000473:pathology; D057131:Immune Evasion; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D051189:Murinae / Q000276:immunology / Q000469:parasitology*; D009569:Nitric Oxide / Q000378:metabolism; D010529:Peritoneal Cavity / Q000469:parasitology*; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism*
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D007074:Immunoglobulin G; D037521:Virulence Factors; D009569:Nitric Oxide