The Granulomatous Inflammatory Response in Jirds, Meriones unguiculatus, to Brugia pahangi: An Ultrastructural and Histochemical Comparison of the Reaction in the Lymphatics and Peritoneal Cavity

Gw, Jeffers; Tr, Klei; Fm, Enright; Wg, Henk

doi:10.2307/3282308

Cited by 33 publications

(23 citation statements)

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“…Presence of granuloma covering the surface of filariae supports the importance of macrophages in anti-filarial immunity [46,47]. We show here that the NF-jB/AP-1 signal in macrophages in response to mf stimulation varies between C57Bl/6 and BALB/c mice and the NF-jB signal is critical for the NOmediated microfilaricidal activity of C57Bl/6 macrophages.…”

Section: Discussionsupporting

confidence: 62%

Poorer NF‐κB signaling by microfilariae in macrophages from BALB/c mice affects their ability to produce cytotoxic levels of nitric oxide to kill microfilariae

et al. 2004

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Upon activation with microfilariae (mf), macrophages from C57Bl/6 mice showed higher nuclear factor-jB (NF-jB) but lower activating protein 1 DNA-binding activity as compared to BALB/c macrophages. The C57Bl/6 macrophages produced cytotoxic levels of nitric oxide (NO) to kill Setaria cervi mf as compared to BALB/c macrophages. Inhibition of the NF-jB signal by pyrrolidine dithiocarbamate (PDTC) blocked NO production and microfilaricidal activity of C57Bl/6 macrophages and inclusion of the exogenous NO generator (SNP) in the PDTC treated C57Bl/6 macrophage cultures induced mf cytotoxicity. These results underscore that the NF-jB signal (induced in response to mf) is important for the NO-mediated microfilaricidal activity of macrophages.

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Section: Discussionsupporting

confidence: 62%

Poorer NF‐κB signaling by microfilariae in macrophages from BALB/c mice affects their ability to produce cytotoxic levels of nitric oxide to kill microfilariae

et al. 2004

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“…Granulomas (with morphology very similar to that which we have described) develop in infected jirds (8), rats (11), golden hamsters (12), and dogs and cats (21). Data on the histopathology of human filarial disease are relatively sparse.…”

Section: Discussionmentioning

confidence: 62%

Kinetics of Cellular Responses to IntraperitonealBrugia pahangiInfections in Normal and Immunodeficient Mice

et al. 2003

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Filarial infections evoke exuberant inflammatory responses in the peritoneal cavities of immunocompetent mice. Clearance of infection appears to be dependent on complex interactions between B1 and B2 B lymphocytes, T cells, eosinophils, macrophages, and the products of these cells. In an earlier communication, we described the course of infection in normal immunocompetent mice. In this study, we utilize mice with well-characterized mutations that disable one or more effector components of adaptive immunity in order to determine their roles in host protection. We characterize peritoneal exudate cells by flow cytometry and determine the kinetics of accumulation of each of the different cell types following infection with Brugia pahangi. We find that (i) fourcolor flow-cytometric analysis of peritoneal exudate cells using anti-CD3, -CD11b, -CD19, and -Gr1 can distinguish up to six different populations of cells; (ii) an initial influx of neutrophils occurs within 24 h of infection, independent of the adaptive immune status of mice, and these cells disappear by day 3; (iii) an early influx of eosinophils is seen at the site of infection in all strains studied, but a larger, second wave occurs only in mice with T cells; (iv) the presence of T cells and eosinophils is important in causing an increase in macrophage size during the course of infection; and (v) most unexpectedly, T-cell recruitment appears to be optimal only if B cells are present, since JHD mice recruit significantly fewer T cells to the site of infection.Mammalian immune responses are remarkably different for different classes of infectious agents. The ensuing inflammatory reaction takes shape with differential recruitment of a variety of cells of the adaptive and innate immune systems. Microorganisms (bacteria and viruses) may be effectively combated by mechanisms such as phagocytosis, neutralization by antibodies, and elimination of infected cells by cytotoxicity. The rules that govern the orchestration of the immune response to and the elimination of large multicellular parasites remain largely unknown. While parasites such as gastrointestinal nematodes can be expelled alive from the body by various mechanisms (5, 6), tissue-dwelling parasites such as filarial nematodes need to be immobilized, sequestered, killed, and disposed of to achieve complete clearance.Filarial parasites are large, metazoan, tissue-dwelling organisms that cause diseases such as lymphatic filariasis, which afflicts over 120 million people in the world (14). Over the past several years, we have used murine models to understand the factors that contribute to host defense. Infection with the feline filarial parasite Brugia pahangi in the peritoneal cavities of laboratory mice evokes an inflammatory reaction. In a recent publication (17), Rajan et al. detailed the time course of Brugia infection in normal, immunocompetent mice and the cellular responses in the peritoneal cavities of these mice. The intent was to use these data to begin to analyze the deviations from such normalcy ...

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“…However, these studies did not establish a quantitative, controllable in vivo model to study the events of early larval migration within mammalian hosts. Brugia species infection in the permissive Mongolian gerbil is well characterized, and the chronic state of infection resembles the microfilaremic asymptomatic state described in many human infections (19,20,25). Here, we utilize this model to further define inflammatory events provoked by L3 in naïve individuals.…”

Section: Discussionmentioning

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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The Granulomatous Inflammatory Response in Jirds, Meriones unguiculatus, to Brugia pahangi: An Ultrastructural and Histochemical Comparison of the Reaction in the Lymphatics and Peritoneal Cavity

Cited by 33 publications

References 0 publications

Poorer NF‐κB signaling by microfilariae in macrophages from BALB/c mice affects their ability to produce cytotoxic levels of nitric oxide to kill microfilariae

Poorer NF‐κB signaling by microfilariae in macrophages from BALB/c mice affects their ability to produce cytotoxic levels of nitric oxide to kill microfilariae

Kinetics of Cellular Responses to IntraperitonealBrugia pahangiInfections in Normal and Immunodeficient Mice

Inflammatory Responses to Migrating Brugia pahangi Third-Stage Larvae

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