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

Gray, Colin; Lawrence, Rachel A.

doi:10.1002/1521-4141(200204)32:4<1114::aid-immu1114>3.0.co;2-b

Cited by 38 publications

(1 citation statement)

References 32 publications

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“…This apparent difference in the impact of clinical pathology on the expression of C1q is obviously due to core differences between the physiopathology of TB and LF. Indeed, since C1q is produced by phagocytotic cells such as macrophages and dendritic cells (Castellano et al 2004; Loos et al 1989), LF worms and microfilaria (> 1100 μm) that are too large to be phagocyted (Gray and Lawrence 2002) may have less impact on the C1q producing phagocytic cells compared to Mycobacterium tuberculosis which persistence mechanism consists in inhibiting the intracellular maturation of phagolysosome in these cells (Ufimtseva et al 2019). Aging is another factor known to affect the expression of C1q (Kouser et al 2015).…”

Section: Discussionmentioning

confidence: 99%

IgG4 antibodies from patients with asymptomatic bancroftian filariasis inhibit the binding of IgG1 and IgG2 to C1q in a Fc-Fc-dependent mechanism

2019

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A striking feature of lymphatic filariasis (LF) is the clinical heterogeneity among exposed individuals. While endemic normals (EN) remain free of infection despite constant exposure to the infective larvae, a small group of patients, generally microfilaria free (Mf-) develops severe pathology (CP) such as lymphedema or hydrocele. Another group of infected individuals remains asymptomatic while expressing large amounts of microfilariae (Mf+). This Mf+ group is characterized by an immune-suppressed profile with high levels of anti-inflammatory cytokines and elevated IgG4. This particular immunoglobulin is unable to activate the complement. The complement system plays a critical role in both innate and adaptive immunity. However, its importance and regulation during LF is not fully understood. Using affinity chromatography and solid-phase-enzyme-immunoassays, we investigated the ability of antibody isotypes from LF clinical groups to bind C1q, the first element of the complement’s classical pathway. The results indicate that while C1q is similarly expressed in all LF clinical groups, IgG1–2 in the plasma from Mf+ individuals presented significantly lower affinity to C1q compared to EN, Mf−, and CP. In addition, selective depletion of IgG4 significantly enhanced the affinity of IgG1–2 to C1q in Mf+ individuals. Strikingly, no effect was seen on the ability of IgG3 to bind C1q in the same conditions. More interestingly, papain-generated IgG4-Fc-portions interacted with Fc portions of IgG1–2 as revealed by far-western blot analysis. These data suggest that while being unable to bind C1q, IgG4 inhibits the first steps of the complement classical pathway by IgG1 or IgG2 via Fc-Fc interactions.Electronic supplementary materialThe online version of this article (10.1007/s00436-019-06451-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

IgG4 antibodies from patients with asymptomatic bancroftian filariasis inhibit the binding of IgG1 and IgG2 to C1q in a Fc-Fc-dependent mechanism

2019

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Eotaxin‐1‐regulated eosinophils have a critical role in innate immunity against experimental Brugia malayi infection

2004

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Using two models of filarial infection in which Brugia malayi microfilariae (Mf) are contained in distinct anatomical compartments, in blood or tissue sites, we have demonstrated a critical role for eotaxin-1 in parasite clearance. In the first model, implantation of adult B. malayi into the peritoneal cavity of eotaxin-1 -/-mice resulted in increased Mf survival associated with a dramatic reduction in peritoneal cavity eosinophilic infiltration. In the second model Mf were injected intravenously into eotaxin-1 -/-mice; Mf clearance from the blood was more rapid than in wild-type mice and was associated with a pronounced blood eosinophilia, resulting from the inability of eosinophils to migrate to tissue sites in the absence of eotaxin-1. (Eotaxin-1 + IL-5) -/-mice had extended Mf survival in the blood and significantly reduced blood eosinophil levels. Interestingly, rapid clearance of a secondary Mf infection following immunization was unaltered in either eotaxin-1 -/-mice or (eotaxin-1 + IL-5) -/-mice. Eosinophil peroxidase levels were high during primary, but not secondary infection, suggesting that eosinophil degranulation is important during primary Mf clearance. Thus, our data show that the presence of eosinophils is critical for innate clearance of B. malayi Mf infection, whereas rapid clearance of secondary infections is independent of both eotaxin-1 and IL-5.

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FcγRs in Health and Disease

Nimmerjahn

Ravetch

2010

Current Topics in Microbiology and Immunology

119

134

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Genetic defects affecting the humoral immune response and especially the production of antibodies of the immunoglobulin G (IgG) isotype result in a heightened susceptibility to infections. Studies over the last years have demonstrated the crucial role of Fc-receptors for IgG (FcγRs) widely expressed on innate immune effector cells in mediating the protective function of IgG. During the last years, additional ligands interacting with FcγRs as well as additional receptors binding to IgG glycosylation variants have been identified. In this review, we discuss how the interaction of these different ligands with classical and novel Fcγ-receptors influences the immune response and which strategies microorganisms have developed to prevent them.

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

Cited by 38 publications

References 32 publications

IgG4 antibodies from patients with asymptomatic bancroftian filariasis inhibit the binding of IgG1 and IgG2 to C1q in a Fc-Fc-dependent mechanism

IgG4 antibodies from patients with asymptomatic bancroftian filariasis inhibit the binding of IgG1 and IgG2 to C1q in a Fc-Fc-dependent mechanism

Eotaxin‐1‐regulated eosinophils have a critical role in innate immunity against experimental Brugia malayi infection

FcγRs in Health and Disease

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