Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Jha, Ruchi; Gangwar, Mamta; Chahar, Dhanvantri; Setty Balakrishnan, Anand; Negi, Mahendra; Misra-Bhattacharya, Shailja
• Is Part Of: Parasites & vectors. Volume 10:Issue 1(2017)
• Page Start: 1
• Page End: 14
• Publication Date: 2017-12
• Subjects: Lymphatic filariasis -- Brugia malayi -- Wolbachia -- Isotype -- Vaccine; Parasitism -- Periodicals; Parasites -- Periodicals; Vector-pathogen relationships -- Periodicals; Animals as carriers of disease -- Periodicals; Insects as carriers of disease -- Periodicals; 616.96
• DOI: 10.1186/s13071-016-1963-x
• Languages: English
• ISSNs: 1756-3305

Abstract

Abstract Background In the past, immune responses to severalBrugia malayi immunodominant antigens have been characterized in filaria-infected populations; however, little is known regardingWolbachia proteins. We earlier cloned and characterized fewB. malayi (trehalose-6-phosphate phosphatase, Bm-TPP and heavy chain myosin, BmAF-Myo) andWolbachia (translation initiation factor-1, Wol Tl IF-1 and NAD+ -dependent DNA ligase, w Bm-LigA) proteins and investigated the immune responses, which they triggered in animal models. The current study emphasizes on immunological characteristics of these proteins in three major categories of filarial endemic zones: endemic normal (EN, asymptomatic, amicrofilaraemic; putatively immune), microfilariae carriers (MF, asymptomatic but microfilaraemic), and chronic filarial patients (CP, symptomatic and mostly amicrofilaraemic). Methods Immunoblotting and ELISA were carried out to measure IgG and isotype antibodies against these recombinant proteins in various clinical categories. Involvement of serum antibodies in infective larvae killing was assessed by antibody-dependent cellular adhesion and cytotoxicity assay. Cellular immune response was investigated by in vitro proliferation of peripheral blood mononuclear cells (PBMCs) and reactive oxygen species (ROS) generation in these cells after stimulation. Results Immune responses of EN and CP displayed almost similar level of IgG to Wol Tl IF-1 while other three proteins had higher serum IgG in EN individuals only. Specific IgA, IgG1, IgG3 and IgM to Bm-TPP were high in EN subjects, while BmAF-Myo additionally showed elevated IgG2. Enhanced IgA and IgG3 were detected in both EN and CP individuals in response to Wol Tl IF-1 antigen, but IgG1 and IgM were high only in EN individuals.w Bm-LigA and BmAF-Myo exhibited almost similar pattern of antibody responses. PBMC isolated from EN subjects exhibited higher proliferation and ROS generation when stimulated with all three proteins except for Wol Tl IF-1. Conclusions Overall, these findings display high immunogenicity of all four proteins in human subjects and revealed that the EN population was exposed to bothB. malayi andWolbachia proteins simultaneously. In addition, immune responses to Wol Tl IF-1 suggest possible role of this factor inWolbachia -induced pathological responses while immune responses to other three proteins suggest that these can be explored further as vaccine candidates.