Impaired clearance of primary but not secondary Brugia infections in IL-5 deficient mice

Ramalingam, Thirumalai R.; Ganley-Leal, Lisa; Porte, Patricia; Rajan, T. V.

doi:10.1016/j.exppara.2003.09.001

Cited by 23 publications

(27 citation statements)

References 31 publications

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“…Thus, even though eosinophil levels were significantly elevated in immunized mice, these cells were apparently not required for killing of the larvae in the adaptive immune response. This observation confirms similar observations with the nematode B. malayi, where eosinophils were required only in the primary response and not in the secondary response (60), and the nematode B. pahangi, where it was observed that IL-5 and presumably eosinophils were required for clearance of primary infections but not secondary infections (48). In contrast to these two studies, eosinophils have been shown to function in adaptive immunity to O. volvulus (1), T. spiralis (65), and L. sigmodontis (43).…”

Section: Vol 74 2006 Eosinophils and Neutrophils In Protective Immusupporting

confidence: 78%

“…There have been previous reports demonstrating that IL-5 or eosinophils participated in primary protective immune responses to the nematodes Strongyloides ratti (68), Strongyloides venezuelensis (19), B. pahangi (48), Brugia malayi (60), and N. brasiliensis (12). In vitro studies have demonstrated that the serum components complement and fibronectin are required for eosinophil binding and degranulation resulting in the killing of N. brasiliensis larvae (58).…”

Section: Discussionmentioning

confidence: 99%

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Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

et al. 2006

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The goal of this study was to determine the roles of eosinophils and neutrophils in innate and adaptive protective immunity to larval Strongyloides stercoralis in mice. The experimental approach used was to treat mice with an anti-CCR3 monoclonal antibody to eliminate eosinophils or to use CXCR2 ؊/؊ mice, which have a severe neutrophil recruitment defect, and then determine the effect of the reduction or elimination of the particular cell type on larval killing. It was determined that eosinophils killed the S. stercoralis larvae in naïve mice, whereas these cells were not required for the accelerated killing of larvae in immunized mice. Experiments using CXCR2؊/؊ mice demonstrated that the reduction in recruitment of neutrophils resulted in significantly reduced innate and adaptive protective immunity. Protective antibody developed in the immunized CXCR2 ؊/؊ mice, thereby demonstrating that neutrophils were not required for the induction of the adaptive protective immune response. Moreover, transfer of neutrophil-enriched cell populations recovered from either wild-type or CXCR2؊/؊ mice into diffusion chambers containing larvae demonstrated that larval killing occurred with both cell populations when the diffusion chambers were implanted in immunized wild-type mice.

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Section: Vol 74 2006 Eosinophils and Neutrophils In Protective Immusupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

et al. 2006

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“…We and others have demonstrated a critical requirement for adaptive immunity in achieving sterile immunity. T cells, B cells, the IL-4 signaling pathway, and IL-5 are essential for efficient elimination of a primary infection (7)(8)(9)(10)(11)(12). We have also demonstrated a crucial role for B1 cells (12,13).…”

Section: Critical Role For Igm In Host Protection In Experimentalmentioning

confidence: 87%

“…Naive or day 14 Brugia-primed PECs were harvested from B6 wt mice and stained for CD11b, CD19, CD3, and IgM. Different cell populations were identified as previously described (2,12). IgM expression on the surface of various cell types is represented as an offset histogram overlay.…”

Section: Discussionmentioning

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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“…Mice were necropsied 2 weeks postinfection. PECs analyzed as described earlier (18) to enumerate lymphocytes and macrophages revealed no significant differences between the two groups. Mice that received anti-CCR3 had significantly fewer eosinophils [(0.57 Ϯ 0.2) ϫ 10 6 cells per mouse] than mice treated with the isotype control antibody [(4.3 Ϯ 1.2) ϫ 10 6 eosinophils per mouse; P Ͻ 0.01].…”

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confidence: 99%

Eosinophils, but Not Eosinophil Peroxidase or Major Basic Protein, Are Important for Host Protection in ExperimentalBrugia pahangiInfection

et al. 2005

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The attenuation of eosinophilia by the administration of monoclonal antibodies to CCR3 consistently correlates with impairment in worm elimination following primary intraperitoneal Brugia pahangi infections in mice. Host protection was unimpaired in mice deficient in eosinophil peroxidase (EPO) or major basic protein 1 (MBP-1), suggesting that eosinophils are essential in host protection but that neither EPO nor MBP-1 alone is.Despite the consistent association of eosinophilia with parasitic infections, evidence supporting a host-protective role in vivo remains elusive (1-4, 16, 22). The function of eosinophils has been studied by modulating their numbers by manipulating interleukin-5 levels (5) (13) or depleting them selectively with a monoclonal antibody against the eotaxin receptor CCR3 (8). Eosinophilia correlates with improved host protection in Angiostrongylus cantonensis (19), Strongyloides ratti (17), Strongyloides stercoralis (12), Onchocerca volvulus (14), and Litomosoides sigmodontis (15) infections. In contrast, the depletion of eosinophils did not alter the course of Schistosoma mansoni (20), Mesocestoides corti (13), and Trichuris muris (3) infections. In the case of filarial parasites, eotaxin and eosinophils have been shown to play a role in host protection (21).The role of eosinophil granule constituents in host protection is also unclear. Purified eosinophil granule proteins have been shown to effectively kill Brugia microfilariae (11), schistosomulae (2), and Trichinella spiralis newborn larvae (10) in vitro. have shown that the death of onchocercal microfilariae following amocarzine treatment was associated with eosinophil degranulation. Electron microscopy analyses showed apposition of eosinophil granule material on the microfilarial surface. However, the requirement of eosinophil granule protein for in vivo host protection has not been studied extensively. In a recent study, EPO Ϫ/Ϫ and wild-type (WT) mice challenged with O. volvulus manifested similar parasite recoveries, suggesting that eosinophil peroxidase (EPO) is not required for host protection in this model (1). In order to investigate the role of the eosinophil granule proteins in host protection, we have now examined the course of Brugia pahangi infection in mice that have undergone targeted mutations in the genes encoding two of the major proteins in the eosinophil granules.C57BL/6 (hereafter WT) mice were obtained from the Jackson Laboratory (Bar Harbor, Maine). EPO Ϫ/Ϫ and MBP-1 Ϫ/Ϫ mice (6, 7) were transferred from the Mayo Clinic, Scottsdale, Arizona, where they were generated and backcrossed with C57BL/6 mice for six generations at the UCHC AAALACaccredited facility. Brugia pahangi third-stage larvae (L3) were provided by one of the following sources: TRS Inc. Monoclonal antibodies against rat RT 6.1 (DS4.23) and 6.2 (6A5) were obtained from Dale Greiner, UMass Medical Center, Worcester, MA. Antibodies were enriched from hybridoma ascites fluid by 50% ammonium sulfate precipitation. The precipitate was dialyzed against phos...

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Impaired clearance of primary but not secondary Brugia infections in IL-5 deficient mice

Cited by 23 publications

References 31 publications

Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

Critical Role for IgM in Host Protection in Experimental Filarial Infection

Eosinophils, but Not Eosinophil Peroxidase or Major Basic Protein, Are Important for Host Protection in ExperimentalBrugia pahangiInfection

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