Microfilaremia and Antibody Responses in CBA/H and CBA/N Mice Following Injection of Microfilariae of Brugia malayi

Thompson, James P.; Crandall, Richard B.; Crandall, Catherine A.; Neilson, J.T.M.

doi:10.2307/3280454

Cited by 27 publications

(17 citation statements)

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“…This defect alone could account for the increased survival of B. malayi Mf in MBL-A Ϫ/Ϫ mice, as a number of previous studies in rodent models of filarial disease have suggested that IgM is critical for Mf clearance (22)(23)(24). Indeed, CBA/N mice, which lack Bruton's tyrosine kinase and peritoneal B1 B cells and are deficient in T-independent type II IgM and IgG3 responses, support both greater Mf survival and increased development of Brugia sp infective larvae (L3) than their WT counterparts (22,23). In addition, mice deficient in circulating IgM (secIgM Ϫ/Ϫ ) have abrogated clearance of primary and secondary L3 infections (25).…”

Section: Discussionmentioning

confidence: 91%

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Carter

Sumiya

Reilly

et al. 2007

The Journal of Immunology

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To investigate the role of mannose-binding lectin-A (MBL-A) in protection against infectious disease, MBL-A−/−-deficient mice were generated. Using a well-characterized mouse model of human filarial nematode infection, nematode survival and protective immune responses were tested in vivo. Blood-borne Brugia malayi microfilariae survived for significantly longer time periods in MBL-A−/− than in wild-type (WT) mice. However, no differences in either splenic cytokine responses or induction of leukocytes in the blood were observed. A profound abrogation of Ag-specific IgM levels was measured in B. malayi-infected MBL-A−/− mice, and some IgG isotypes were higher than those observed in WT animals. To establish whether there was a defect in Ab responses per se in MBL-A−/− mice or the effect was specific to filarial infection, we immunized these mice with OVA or a carbohydrate-free protein. Significantly, Ag-specific IgM responses were defective to both of these Ags, and Ag-specific IgG responses were largely unaffected. Furthermore, in naive mice, total IgM levels did not differ between MBL-A−/− and WT mice. This article describes the first demonstration that MBL-A may function independently of MBL-C and suggests that MBL-A, like other C-type lectins and members of the complement cascade, is intimately involved in the priming of the humoral Ab response.

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Section: Discussionmentioning

confidence: 91%

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Carter

Sumiya

Reilly

et al. 2007

The Journal of Immunology

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“…In multiple independent experiments, the concentration of LPS needed to generate equivalent induction went up by 6-fold for TNF-␣ and 10-fold for IL-1␤ ( p Ͻ 0.001) for xid macrophages over wild-type cells. Because these proinflammatory cytokines are also known to be directly cytotoxic for a number of parasitic pathogens (45)(46)(47), it was possible that they could be contributing to the delayed mf clearance observed in xid mice (16,50).…”

Section: Poor Induction Of Proinflammatory Cytokines In Xid Macrophagesmentioning

confidence: 99%

Macrophage Effector Functions Controlled by Bruton’s Tyrosine Kinase Are More Crucial Than the Cytokine Balance of T Cell Responses for Microfilarial Clearance

Mukhopadhyay

Mohanty

Mangla

et al. 2002

The Journal of Immunology

100

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Macrophages from X-linked immunodeficient (xid) mice lacking functional Bruton’s tyrosine kinase (Btk) show poor NO induction and enhanced IL-12 induction, and contribute to delayed clearance of injected microfilaria (mf) in vivo. We now show that Btk is involved in other macrophage effector functions, such as bactericidal activity and secretion of proinflammatory cytokines (TNF-α, IL-1β), but not the T cell-directed cytokine IL-12. Induction of some transcriptional regulators of the NF-κB family, crucial for the expression of proinflammatory cytokines, is also poor in Btk-deficient macrophages. Thus, Btk appears to be involved in signaling for inducible effector functions, but not APC functions, in macrophages. Furthermore, adoptive transfer of T cells from mf-infected xid or wild-type mice did not alter the course of mf clearance in recipients, mf clearance was unaltered in IFN-γ-deficient mice, and improved mf clearance was seen only if greater inducibility of IL-12 was accompanied by greater NO secretion from macrophages, as seen in Ityr C.D2 mice as compared with congenic Itys BALB/c mice. Thus, delayed mf clearance in xid mice was correlated not with the high IL-12/Th1 phenotype but with low NO induction levels. Also, xid macrophages showed poor toxicity to mf in vitro as compared with wild-type macrophages. Inhibition of NO production blocked this mf cytotoxicity, and an NF-κB inhibitor blocked both NO induction and mf cytotoxicity. Thus, Btk is involved in inducing many macrophage effector functions, and delayed mf clearance seen in Btk-deficient xid mice is due to poor NO induction in macrophages, resulting in compromised microfilarial toxicity.

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“…Duration of microfilaraemia varies in different mouse strains and is known to be independent of MHC haplotype and inherited in a dominant fashion [18] Absence of btk in other filarial nematode systems has shown that life-span of Mf is greatly extended in xid mice [7,8,16]. A study of Setaria digitata in BALB/c xid mice showed that extended Mf survival correlated with elevated Type 1 responses [16].…”

Section: Discussionmentioning

confidence: 99%

“…In addition the presence of anti-Mf sheath Ab has been shown to correlate with amicrofilaraemia in people from an endemic area [5]. In some animal model studies, a correlation between the presence of anti-Mf Ab and Mf clearance has also been shown in vivo [6][7][8]. Additionally, in vitro, Ab and complement (C) from both human hosts and animal models can mediate effector cell adhesion and, in some cases, killing of Brugia and Wuchereria Mf [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

A role for antibody and Fc receptor in the clearance ofBrugia malayi microfilariae

Gray

Lawrence

2002

Eur. J. Immunol.

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Microfilaremia and Antibody Responses in CBA/H and CBA/N Mice Following Injection of Microfilariae of Brugia malayi

Cited by 27 publications

References 0 publications

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Macrophage Effector Functions Controlled by Bruton’s Tyrosine Kinase Are More Crucial Than the Cytokine Balance of T Cell Responses for Microfilarial Clearance

A role for antibody and Fc receptor in the clearance ofBrugia malayi microfilariae

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