Infectivity and Normal Development of Third Stage Brugia malayi Maintained In vitro

Ja, Yates; Ka, Schmitz; Fk, Nelson; Tv, Rajan

doi:10.2307/3283436

Cited by 16 publications

(7 citation statements)

References 8 publications

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“…Infectious larvae. Brugia pahangi L3 was harvested at either TRS Inc., Athens, GA, the University of Georgia (John McCall), or the University of Louisiana (Thomas Klei) from infected Aedes aegypti mosquitoes and transported in RPMI supplemented with antibiotics as described previously (18).…”

Section: Methodsmentioning

confidence: 99%

Granuloma Formation around Filarial Larvae Triggered by Host Responses to an Excretory/Secretory Antigen

et al. 2011

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In previous studies using a murine model of filarial infection, granuloma formation was found to be a most important host-protective mechanism. We have also shown that in vitro cytoadherence is a surrogate for the formation of antifilarial granulomas in vivo and that it requires "alternatively activated" host cells and a source of antifilarial antibody. We show here that antibodies against L3 excretory/secretory (E/S) products can facilitate in vitro cytoadherence. We generated a set of hybridomas reactive with filarial E/S products and screened them for their ability to mediate in vitro cytoadherence. One clone (no. 1E9) was positive in this assay. We then screened a novel expression library of filarial antigens displayed on the surface of T7 bacteriophage for reactivity with 1E9. Phage expressing two filarial antigens (TCTP and BmALT-2) reacted with 1E9. Immunization of mice showed that the cohort immunized with BmALT-2 cleared a challenge infection with infective Brugia pahangi L3 in an accelerated manner, whereas cohorts immunized with TCTP cleared larvae with the same kinetics as in unimmunized mice. These data confirm that BmALT-2 is the antigenic target of granuloma-mediated killing of B. pahangi L3. Our findings also confirm previous studies that BmALT-2 is a potential vaccine candidate for filarial infection. Our data reinforce the work of others and also provide a possible mechanism by which immune responses to BmALT-2 may provide host protection.

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Section: Methodsmentioning

confidence: 99%

Granuloma Formation around Filarial Larvae Triggered by Host Responses to an Excretory/Secretory Antigen

et al. 2011

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“…B. pahangi L3 organisms were harvested at the insectarium of TRS Inc., Athens, Ga., or the University of Georgia from infected Aedes aegypti mosquitoes and shipped in Ham's complete medium as described previously (26).…”

Section: Methodsmentioning

confidence: 99%

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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“…Brugia pahangi L3 were harvested at TRS Inc. (Dr. J. McCall, University of Georgia, Athens, GA) or the University of Louisiana (Dr. T. Klei) from infected Aedes aegytpi mosquitoes and transported in RPMI 1640 supplemented with antibiotics as described previously (22).…”

Section: Infectious Larvaementioning

confidence: 99%

Critical Role for IgM in Host Protection in Experimental Filarial Infection

Rajan

Ramalingam

Rajan

2005

The Journal of Immunology

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We have previously shown that B cells (in particular B1 cells) are important in host protection against brugian infections in a murine i.p. model. In this study, we show that mice deficient in circulating IgM (secIgM−/−), but otherwise normal in their humoral responses, manifest a significant impairment in worm elimination, suggesting that one critical B cell function is the production of Ag-specific IgM. Efficient elimination of larvae is IgM dependent for both primary and challenge infections. The ability to eliminate worms is restored in secIgM−/− mice by administering sera from primed mice. We corroborated these in vivo studies with in vitro observations which show that IgM is the only isotype that reacts strongly with the surface of Brugia L3. Furthermore, activated peritoneal exudate cells adhere to L3 only in the presence of filaria-specific sera or IgM purified from them. This attachment is not reduced by heat inactivation of the serum, suggesting complement independent activity. Peritoneal exudate cells from primed mice, especially activated macrophages, carry high levels of IgM on their surfaces. Our observations suggest that an IgM-mediated reaction initiates the formation of host-protective granulomas.

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Infectivity and Normal Development of Third Stage Brugia malayi Maintained In vitro

Cited by 16 publications

References 8 publications

Granuloma Formation around Filarial Larvae Triggered by Host Responses to an Excretory/Secretory Antigen

Granuloma Formation around Filarial Larvae Triggered by Host Responses to an Excretory/Secretory Antigen

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

Critical Role for IgM in Host Protection in Experimental Filarial Infection

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