Brugia pahangi Infections in Mongolian Jirds and Dogs Following the Ocular Inoculation of Infective Larvae

Ah, Hyong-Sun; Klei, Thomas R.; McCall, John W.; Thompson, Paul E.

doi:10.2307/3278729

Cited by 12 publications

(7 citation statements)

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“…Laboratory animal models are uniquely suited to examining these questions. Previous studies have examined early filarial infection events, including parasite transfer from vector to host (16) and early larval recoveries prior to adult establishment in the lymphatics (1,3,5). However, these studies did not establish a quantitative, controllable in vivo model to study the events of early larval migration within mammalian hosts.…”

Section: Discussionmentioning

confidence: 99%

“…These events have been demonstrated experimentally by feeding Brugia-infected mosquitoes on cats (14,17) and gerbils (3) and by in vivo studies involving the application of L3 to punctured skin (14). Furthermore, previous studies by Ah et al (1) have clearly shown that L3 can actively and rapidly migrate through a variety of complex tissues following placement on the surface of the gerbil eyeball. The mechanisms utilized by the larvae during this early migratory phase through these various tissues have not been defined.…”

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confidence: 92%

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Inflammatory Responses to Migrating Brugia pahangi Third-Stage Larvae

et al. 2006

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Despite being central to parasite establishment and subsequent host pathological and immunologic responses, host-parasite interactions during early third-stage filarial larva (L3) migration are poorly understood. These studies aimed to define early tissue migration of Brugia pahangi L3 in the gerbil (Meriones unguiculatus) and measure host cellular responses during this period. Gerbils were intradermally inoculated in the hind limb with 100 B. pahangi L3, and necropsies were performed at various times. At 3 h, most L3 (96.3%) were recovered from tissues associated with the infection site, with marked L3 migration occurring by 24 h. Larvae were dispersed throughout the lymphatics at 7 days postinfection (dpi), and at 28 dpi, most parasites were recovered from the spermatic cord lymphatics. Parasites were identified histologically at all time points. Inflammatory cells, primarily neutrophils, were frequently observed around larvae in the dermis and muscle near the injection site at 3 h and 24 h. Levels of interleukin-6 (IL-6) and tumor necrosis factor-␣ mRNA peaked at 3 h in all tissues, with IL-6 levels also high in the spleen at 28 dpi. Levels of IL-4 mRNA were elevated in all tissues at 28 dpi. These observations demonstrate that L3 migrate quickly through various tissues and into lymph nodes in a predictable pattern. Migrating L3 induce an early acute inflammatory response that is modulated as parasites establish in the lymphatics. Polarization of the host response towards a dominant Th2-like profile is present at 7 dpi and is well established by 28 dpi in this permissive host.It is generally accepted that third-stage filarial nematode infective larvae (L3) emerge from the mosquito labia during feeding, accumulate in a pool of hemolymph, and enter the host through the wound left by the mosquito vector (13). While the L3 are apparently unable to penetrate intact skin, their early migrations require movements through the connective tissues of the skin to lymphatic vessels and, in some cases, the blood vascular system. These events have been demonstrated experimentally by feeding Brugia-infected mosquitoes on cats (14, 17) and gerbils (3) and by in vivo studies involving the application of L3 to punctured skin (14). Furthermore, previous studies by Ah et al. (1) have clearly shown that L3 can actively and rapidly migrate through a variety of complex tissues following placement on the surface of the gerbil eyeball. The mechanisms utilized by the larvae during this early migratory phase through these various tissues have not been defined.Early migrations of L3 through the tissues of the skin not only are central to the successful establishment of parasites but are also likely to be important in the initial induction of the host response. It is expected that these responses are involved in the elimination or inhibition of incoming L3 during early migrations. The migration of L3 into the skin may also be uniquely involved in defining the nature of subsequent immune responses to parasite antigens. Based on various in ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 92%

Inflammatory Responses to Migrating Brugia pahangi Third-Stage Larvae

et al. 2006

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“…L3s penetrate the cornea, and within 5 min, some can be found in the pleural cavity, where the majority of worms will eventually localize (93). This induces a relatively low-level microfilaremia, which may be due to the necessity of MF to penetrate capillaries before entering the circulation (93).…”

Section: Morris Et Almentioning

confidence: 99%

“…i.p. injection enables easier collection and counting of worms, as over 90% of surviving larvae remain and develop within the peritoneal cavity (88,90,93). Despite being a more effective route for establishment of adult worm infections, worm localization and pathological sequelae after i.p.…”

Section: Morris Et Almentioning

confidence: 99%

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

et al. 2013

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SUMMARY Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. In this review, we have organized, to the best of our ability, all published filaria vaccine trials and reviewed them in the context of the animal models used. Additionally, we provide information on the life cycle, disease phenotype, concomitant immunity, and natural immunity during primary and secondary infections for 24 different filaria models.

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“…and the inflammatory lesions associated with lymphatic filariasis (1,2,16,21,27,32,37,38). Gerbils develop chronic infections with B. pahangi that result in lymphatic damage through the formation of well-characterized granulomatous lesions (21,54).…”

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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 )

Chirgwin¹,

Coleman²,

Porthouse³

et al. 2003

Infect Immun

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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...

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Brugia pahangi Infections in Mongolian Jirds and Dogs Following the Ocular Inoculation of Infective Larvae

Cited by 12 publications

References 7 publications

Inflammatory Responses to Migrating Brugia pahangi Third-Stage Larvae

Inflammatory Responses to Migrating Brugia pahangi Third-Stage Larvae

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

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 )

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