Response In Filariasis Research Articles

Self-reactive IgG4 antibodies are associated with blocking of pathology in human lymphatic filariasis

Lymphatic filariasis, a chronic disfiguring disease exhibits complex pathology. Based on different clinical manifestations, infected individuals are categorized into asymptomatic-carriers and chronic-patients. The mechanism behind differential clinical outcomes remains unclear. Roles of filaria-specific B cell responses in filariasis have been documented, whereas the contribution of B1 cell response and poly-specific IgG and IgA in the context of clinical filariasis is not deciphered. In this study, we measured the poly-specific IgG and IgA levels in different clinical categories of filariasis. Asymptomatic-carriers exhibited increased IgG4 antibodies against both filarial-antigens as well as auto-antigens compared to other clinical categories, although IgG against these auto-antigens remained lower. IgA levels against both filarial and auto-antigens were decreased in asymptomatic-carriers. A positive correlation between anti-filarial IgG4 and IgG4 against auto-antigens were observed, suggesting the synergistic role of poly-specific natural IgG4 with anti-filarial IgG4 in blocking the pathogenesis in asymptomatic microfilarial cases.

Diminished Expression and Function of TLR in Lymphatic Filariasis: A Novel Mechanism of Immune Dysregulation

Lymphatic filariasis is a disease characterized by immune dysregulation involving APC and T cell populations. To assess the contribution of TLR in mediating this dysregulation, we examined the expression of TLR1, TLR2, TLR4, and TLR9 on B cells and monocytes of filaria-infected and uninfected individuals. Baseline expression of TLR was significantly lower in B cells but not in monocytes of the filaria-infected group compared with the uninfected group. Upon stimulation with filarial Ag, a diminished up-regulation of TLR was observed in both B cells and monocytes of infected individuals. Finally, stimulation of B cells and monocytes with TLR ligands resulted in decreased B cell and monocyte activation/cytokine production, indicating a state of immune tolerance. This dysregulation is associated with diminished CD4(+) T cell production of IFN-gamma and IL-5. The diminished expression and function of TLR is thus a likely consequence of chronic Ag stimulation and could serve as a novel mechanism underlying the dysfunctional immune response in filariasis.

Human antibody responses to Brugia malayi antigens in brugian filariasis

Human antibody responses to Brugia malayi antigens were studied with sera from a Brugia endemic area in South India. Patients with clinical filariasis had significantly higher IgE and lower IgG4 levels to adult worm antigens than people with asymptomatic microfilaraemia. Intermediate antibody levels were observed in endemic normals. A majority of sera from each clinical group contained IgG antibodies to surface antigens of infective larvae (L3) by IFAT. IgG immunoblot studies did not reveal group differences in L3 antigen recognition. IgE antibodies bound to a subset of antigens bound by IgG. IgE antibodies in sera from clinical filariasis patients preferentially bound to L3 antigens at 200, 97, 68 and 58 kDa compared with sera from microfilaria carriers. These results are consistent with prior studies of antibody responses in filariasis and add new information on the targets of IgG and IgE antibodies to L3 antigens in brugian filariasis.

Life Cycle of Brugia pahangi (Nematoda) in Nude Mice, C3H/HeN (nu/nu)

The development of Brugia pahangi (Nematoda: Filarioidea) was studied in nude (congenitally athymic) mice C3H/HeN (nu/nu) and in their phenotypically normal littermates (nu/+). Nude mice were highly susceptible to this parasite. As in the natural host (the cat), the nematodes' third molt in nude mice occurred at 7 to 10 days. The final molt occurred at about 24 days for male worms and 33 days for female worms. Adult worms were smaller than those from other hosts, such as the cat. After inoculation of various numbers of infective larvae, recoveries of adult worms averaged about 15% of the inoculum. In long-term infections initiated with 100 larvae, about 75% of the worms localized in the heart or lungs. Patent infections were seen as early as day 50 PI. Microfilaremia developed in most nude mice given 100, 50, or 25 infective larvae, but was less frequent in those given only 10. Mean filaremias generally rose during the first 6 mo, but in individuals usually did not exceed 500-600/20 mm3 of blood. As in the Mongolian jird, intraperitoneal inoculations yielded large quantities of worms and microfilariae. Few worms could be recovered from normal mice after day 40, even when large (1,000 larvae) inocula were used. Microfilaremia was not detected in normal mice. Although recoveries of adult worms from some nude females were not as high as those from nude males, neither nude nor normal mice showed consistent evidence of a differential susceptibility based on sex. Given the strong, consistent dichotomy of response to B. pahangi between nude and normal mice, this system may be useful in studies of protective immune responses in filariasis.