Protective Immunity in Human Filariasis: A Role for Parasite‐Specific IgA Responses

Sahu, Bikash; Mohanty, Madhu Chhanda; Sahoo, Prakash Kumar; Satapathy, Alok; Ravindran, Balachandran

doi:10.1086/589881

Cited by 26 publications

(23 citation statements)

References 43 publications

(39 reference statements)

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“…Apart from IgG antibody, protein specific serum IgA and IgM were also in higher concentration in EN group while all MF individuals contained low antibody reactivity and CP had moderate. A protective role for IgA has been reported for several helminthic infections such as Schistosoma mansoni , Taenia taeniformis , Trichinella spiralis , including cattle filarial parasite Setaria digitata [38–41]. Protective role of IgM has also been postulated in Strongyloides stercoralis , Brugia phangi and W. bancrofti infections [37, 42, 43] .…”

Section: Discussionmentioning

confidence: 99%

Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

et al. 2017

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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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1963-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

et al. 2017

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“…Naturally occurring amicrofilaremic individuals have been documented in filarial-infected humans with O. volvulus [63], W. bancrofti [29, 64, 65], B. malayi [29, 62, 66], and B. pahangi [66], and in dogs infected with D. immitis [47, 67–70]. Wong & Suter [67] noted that when naturally amicrofilaremic D. immitis- infected dogs were treated to remove adult worms and then re-infected, the dogs were susceptible to subsequent infection, but the new infection was also amicrofilaremic.…”

Section: Administration To Filarial Wormsmentioning

confidence: 99%

“…Mammalian hosts are also naturally capable of creating antibody responses to the surface proteins and secretory proteins of larval (L3 and L4) and adult stages of filarial worms [29, 65, 71–77]. These filarial proteins are presented to the host’s immune system through secretions, molting, or the deaths of developing larvae as they migrate through the tissue of the host, or adult worms wherever they reside.…”

Section: Administration To Filarial Wormsmentioning

confidence: 99%

Examining the role of macrolides and host immunity in combatting filarial parasites

Carithers

2017

Parasites Vectors

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Macrocyclic lactones (MLs), specifically the avermectins and milbemycins, are known for their effectiveness against a broad spectrum of disease-causing nematodes and arthropods in humans and animals. In most nematodes, drugs in this class induce paralysis, resulting in starvation, impaired ability to remain associated with their anatomical environment, and death of all life stages. Initially, this was also thought to be the ML mode of action against filarial nematodes, but researchers have not been able to validate these characteristic effects of immobilization/starvation of MLs in vitro, even at higher doses than are possible in vivo. Relatively recently, ML receptor sites exclusively located proximate to the excretory-secretory (ES) apparatus were identified in Brugia malayi microfilaria and an ML-induced suppression of secretory protein release by B. malayi microfilariae was demonstrated in vitro. It is hypothesized here that suppression of these ES proteins prevents the filarial worm from interfering with the host’s complement cascade, reducing the ability of the parasite to evade the immune system. Live microfilariae and/or larvae, thus exposed, are attacked and presented to the host’s innate immune mechanisms and are ultimately killed by the immune response, not the ML drug. These live, exposed filarial worms stimulate development of innate, cellular and humoral immune responses that when properly stimulated, are capable of clearing all larvae or microfilariae present in the host, regardless of their individual sensitivity to MLs. Additional research in this area can be expected to improve our understanding of the relationships among filarial worms, MLs, and the host immune system, which likely would have implications in filarial disease management in humans and animals.

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Section: Discussionmentioning

confidence: 99%

“…Recently in human bancroftian filariasis, the role of IgA in protective immunity has been demonstrated [54]. IgA levels in mice have directly been found to be associated with raised interferon gamma (IFN- γ ) production by T cells [10, 54]. The role of IgM, remains undefined in nematodes; however, in vitro, it has been shown to play a major role in adherence of host immune cells to filarial L3 and Mf causing cytotoxicity and their death [55].…”

Section: Discussionmentioning

confidence: 99%

Cofactor Independent Phosphoglycerate Mutase ofBrugia malayiInduces a Mixed Th1/Th2 Type Immune Response and Inhibits Larval Development in the Host

Singh

Kushwaha

Rana

et al. 2014

BioMed Research International

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Lymphatic filariasis is a major debilitating disease, endemic in 72 countries putting more than 1.39 billion people at risk and 120 million are already infected. Despite the significant progress in chemotherapeutic advancements, there is still need for other measures like development of an effective vaccine or discovery of novel drug targets. In this study, structural and immunological characterization of independent phosphoglycerate mutase of filarial parasite Brugia malayi was carried out. Protein was found to be expressed in all major parasite life stages and as an excretory secretory product of adult parasites. Bm-iPGM also reacted to all the categories of human bancroftian patient's sera including endemic normals. In vivo immunological behaviour of protein was determined in immunized BALB/c mice followed by prophylactic analysis in BALB/c mice and Mastomys coucha. Immunization with Bm-iPGM led to generation of a mixed Th1/Th2 type immune response offering 58.2% protection against larval challenge in BALB/c and 65–68% protection in M. coucha. In vitro studies confirmed participation of anti-Bm-iPGM antibodies in killing of B. malayi infective larvae and microfilariae through ADCC mechanism. The present findings reveal potential immunoprotective nature of Bm-iPGM advocating its worth as an antifilarial vaccine candidate.

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Protective Immunity in Human Filariasis: A Role for Parasite‐Specific IgA Responses

Cited by 26 publications

References 43 publications

Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

Examining the role of macrolides and host immunity in combatting filarial parasites

Cofactor Independent Phosphoglycerate Mutase ofBrugia malayiInduces a Mixed Th1/Th2 Type Immune Response and Inhibits Larval Development in the Host

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