Removal of Wolbachia from Brugia pahangi Is Closely Linked to Worm Death and Fecundity but Does Not Result in Altered Lymphatic Lesion Formation in Mongolian Gerbils ( Meriones unguiculatus )

Abstract

Approximately 30 years ago, researchers reported intracellular bacteria in filarial nematodes. These bacteria are relatives of the arthropod symbiont Wolbachia and occur in many filarial nematodes, including Brugia pahangi and Brugia malayi. Wolbachia bacteria have been implicated in a variety of roles, including filaria development and fecundity and the pathogenesis of lymphatic lesions associated with filarial infections. However, the role of the bacteria in worm biology or filarial disease is still not clear. The present experiments support previous data showing that tetracycline eliminates or reduces Wolbachia bacteria in B. pahangi in vivo. The elimination of Wolbachia was closely linked to a reduction in female fecundity and the viability of both sexes, suggesting that the killing of Wolbachia is detrimental to B. pahangi. The gerbils treated with tetracycline showed reduced levels of interleukin-4 (IL-4) and IL-5 mRNA in renal lymph nodes and spleens compared with the levels in B. pahangi-infected gerbils not treated with tetracycline. However, similar findings were noted in B. pahangi-infected gerbils treated with ivermectin, suggesting that the loss of circulating microfilariae, not the reduction of Wolbachia bacteria, was associated with the altered cytokine profile. Despite the change in T-cell cytokines, there was no difference in the sizes of renal lymph nodes isolated from gerbils in each treatment group. Furthermore, the numbers, sizes, or cellular compositions of granulomas examined in the lymphatics or renal lymph nodes did not differ with treatment. These data suggest that Wolbachia may not play a primary role in the formation of lymphatic lesions in gerbils chronically infected with B. pahangi.Lymphatic filariasis is caused primarily by the filarial nematodes Wuchereria bancrofti and Brugia malayi and affects more than 120 million people throughout the tropics and subtropics. The disease presents as a broad range of clinical and subclinical symptoms, including fever, acute and chronic inflammation, lymphatic edema, and elephantiasis. While much research has focused on the disease caused by infection with Brugia or Wuchereria, the mechanism(s) underlying the pathogenesis of lymphatic filariasis has not been clearly defined. In both acute and chronic infections, these mechanisms probably involve a diverse range of inflammatory reactions attributable to the parasite, host inflammatory responses, and opportunistic infections (40).Approximately 30 years ago, several researchers reported intracellular bacteria in filarial nematodes (31, 37, 54). These bacteria have since been identified as relatives of the arthropod symbiont Wolbachia (46). Wolbachia bacteria have now been reported to exist in many filarial nematodes, including B. malayi and Brugia pahangi (3,30,49,55). Interestingly, Wolbachia has recently been proposed to play a role in the induction of the host immune response to filariae (9,44,50,51). Some researchers suggest that lipopolysaccharide (LPS)-like molecules from filarial Wolbachia b...

Effects of gamma radiation on Brugia malayi infective larvae and their intracellular Wolbachia bacteria

“…The present study showed that jirds infected with normal B. malayi L3 did not develop antibodies to Wolbachia wsp until the onset of microfilarial patency. This result was consistent with results reported in studies of B. pahangi (Chirgwin et al 2003). Wolbachia densities in worms appear to multiply Jirds vaccinated with irradiated L3 were largely immune to challenge infections, as expected.…”

Use of liposomized tetracycline in elimination ofWolbachiaendobacterium of human lymphatic filariidBrugia malayiin a rodent model

“…This data supports the earlier reports of no incidental effect of antibiotic on natural filarial infections by conventional periods of antibiotic therapy (3 -5 days) and thus, there is a substantial requirement of longer periods of treatment (Bandi et al 2001). Reports from other groups have demonstrated clearance of bacteria after 76 days continuous treatment but the effect on worm recovery could be seen only if treatment was continued for at least 86 -100 days (Chirgwin et al 2003). Therefore, the treatment schedule in the present study was extended upto 90 and 120 days to ensure complete elimination of endobacteria from the worms that in turn ensure elimination of filarial parasite.…”

Stage-specific proteomic expression patterns of the human filarial parasiteBrugia malayiand its endosymbiontWolbachia

“…The presence of complete pathways for nucleotide and heme biosynthesis in Wolbachia and their partial absence in the filarial parasites, coupled with the observation of a loss of viability and reproductive capacity of the filarial organisms following elimination of Wolbachia by antibiotics (42)(43)(44), suggest that the endosymbiont provides crucial signals and pathway components critical for parasite survival. Interestingly, all the members of the heme biosynthetic pathway, except for the ferrochelatase (Wbm0719) and the protoporphyrinogen oxidase, which is absent from the Wolbachia genome, were detected in the present proteomic analysis.…”