Infection Outcome and Cytokine Gene Expression inBrugia pahangi- Infected Gerbils (Meriones unguiculatus) Sensitized withBrucella abortus

Chirgwin, Sharon R.; Elzer, Philip H.; Coleman, Sharon U.; Nowling, Jena M.; Hagius, Sue D.; Edmonds, Matthew D.; Klei, Thomas R.

doi:10.1128/iai.70.11.5938-5945.2002

Cited by 17 publications

(18 citation statements)

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“…The Brugia pahangi (Bp)-infected gerbil serves as a model to mimic endemic filarial infection of humans [14–17]. Bp produces a chronic parasitism in the gerbil when injected subcutaneously, characterized by a microfilaremia and a Th2-mediated immune response [16,18,19]. …”

Section: Introductionmentioning

confidence: 99%

Brugia filariasis differentially modulates persistent Helicobacter pylori gastritis in the gerbil model

Martin

Shakya

Muthupalani

et al. 2010

Microbes and Infection

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In select Helicobacter pylori-infected populations with low gastric cancer, nematode coinfections are common and both helicobacter gastritis and filariasis are modeled in gerbils. We evaluated gastritis, worm counts, tissue cytokine gene expression levels and Th1/Th2-associated antibody responses in H. pylori and Brugia pahangi mono- and coinfected gerbils. H. pylori-associated gastritis indices were significantly lower 21 weeks post-infection in coinfected gerbils (p ≤ 0.05) and were inversely proportional to worm counts (r2 = −0.62, p < 0.003). Additionally, IFN-γ, IL-1β, CXCL1, IL-4 and IL-10 mRNA levels in the gastric antrum reflected a significant host response to gastric H. pylori and as well as systemic filariasis (p ≤ 0.05). Despite increasing worm burden (p < 0.05), gastritis progressed in coinfected gerbils (p < 0.03) becoming equivalent to H. pylori-infected gerbils at 42 weeks (p = 0.7). Pro- and anti-inflammatory mediator mRNA levels were notably downregulated in B. pahangi infected gerbils below uninfected control values, suggesting hyporesponsiveness to B. pahangi. Consistent with an increasing Th1 response to H. pylori, IgG2a (p < 0.01), IL-1β (p = 0.04) and CXCL1 (p = 0.006) responses significantly increased and IL-4 (p = 0.05) and IL-10 (p = 0.04) were decreased in coinfected gerbils at 42 weeks. Initial systemic responses to B. pahangi resulted in attenuated gastritis in coinfected gerbils, but subsequent filarid-associated hyporesponsiveness appears to have promoted H. pylori gastritis.

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Section: Introductionmentioning

confidence: 99%

Brugia filariasis differentially modulates persistent Helicobacter pylori gastritis in the gerbil model

Martin

Shakya

Muthupalani

et al. 2010

Microbes and Infection

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“…; PE Biosystems). All cDNA and oligonucleotide sequences have been previously described (11,33,34,35). Primers were unlabeled, and probes were labeled with the reporter dye 6-FAM (6-carboxyfluorescein) and the quencher dye TAMRA (6-carboxytetramethylrhodamine).…”

Section: Gerbils and Parasitesmentioning

confidence: 99%

“…All PCR analyses were carried out in duplicate. Relative standard curves were constructed using cDNA prepared from spleen cells stimulated with concanavalin A (10 g/ml) for 24 h (11,29). Data are presented as the mean fold change for a treatment group compared with the mean value for the control group (ϮSE).…”

Section: Gerbils and Parasitesmentioning

confidence: 99%

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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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“…Relative standard curves were constructed from cDNA prepared from RNA isolated from cells stimulated with either concanavalin A (10 g/ml, 24 h) (10,22) or lipopolysaccharide (LPS) (10 g/ml) (22). The concanavalin A-stimulated cDNA was used as a standard for IL-4 and IFN-␥, and the LPS-stimulated cDNA was used for TNF-␣ and IL-6.…”

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confidence: 99%

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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Infection Outcome and Cytokine Gene Expression inBrugia pahangi- Infected Gerbils (Meriones unguiculatus) Sensitized withBrucella abortus

Cited by 17 publications

References 53 publications

Brugia filariasis differentially modulates persistent Helicobacter pylori gastritis in the gerbil model

Brugia filariasis differentially modulates persistent Helicobacter pylori gastritis in the gerbil model

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 )

Inflammatory Responses to Migrating Brugia pahangi Third-Stage Larvae

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