Abstract
BackgroundIn the past, immune responses to several Brugia malayi immunodominant antigens have been characterized in filaria-infected populations; however, little is known regarding Wolbachia proteins. We earlier cloned and characterized few B. malayi (trehalose-6-phosphate phosphatase, Bm-TPP and heavy chain myosin, BmAF-Myo) and Wolbachia (translation initiation factor-1, Wol Tl IF-1 and NAD+-dependent DNA ligase, wBm-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).MethodsImmunoblotting 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.ResultsImmune 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. wBm-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.ConclusionsOverall, these findings display high immunogenicity of all four proteins in human subjects and revealed that the EN population was exposed to both B. malayi and Wolbachia proteins simultaneously. In addition, immune responses to Wol Tl IF-1 suggest possible role of this factor in Wolbachia-induced pathological responses while immune responses to other three proteins suggest that these can be explored further as vaccine candidates.
Highlights
In the past, immune responses to several Brugia malayi immunodominant antigens have been characterized in filaria-infected populations; little is known regarding Wolbachia proteins
Reactivity of W. bancrofti serum antibodies with B. malayi and Wolbachia recombinant proteins Seventy nine human serum samples including NEN (10), EN (24), MF (21) and Chronic patients (CP) (24) were tested individually for antibody reactivity with all the four recombinant proteins in Western blotting using anti-human IgG-HRP as secondary antibody
All of the 24 CP sera were positive for anti-Wol Tl IF-1 and antiwBm-LigA antibodies, but BmAF-Myo reacted with only 23 of these and Brugia malayi trehalose-6-phosphate phosphatase (TPP) (Bm-TPP) with only 22
Summary
Immune responses to several Brugia malayi immunodominant antigens have been characterized in filaria-infected populations; little is known regarding Wolbachia proteins. Human lymphatic filariasis (LF) is a debilitating disease caused by Wuchereria bancrofti, Brugia malayi and Brugia timori and transmitted through mosquitoes. Wuchereria bancrofti, the most prevalent species worldwide, is responsible for about 80% of the infection in the endemic areas, while B. malayi and B. timori are less prevalent [1]. Mass drug administration of albendazole in conjunction with diethylcarbamazine or ivermectin is recommended for controlling LF [4]. These strategies have limitations associated with repeated administration of conventional drugs due to limited adulticidal activity and reports of development of drug resistance. Discovery of new macrofilaricidal drug or a potent vaccine would be an appropriate complementary approach to control human bancroftian filariasis
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