Natural antibodies sustain differentiation and maturation of human dendritic cells

Bayry, Jagadeesh; Lacroix‐Desmazes, Sébastien; Donkova-Petrini, Vladimira; Carbonneil, Cédric; Misra, Namita; Lepelletier, Yves; Delignat, Sandrine; Varambally, Sooryanarayana; Oksenhendler, Éric; Lévy, Yves; Debré, Marianne; Kazatchkine, Michel D.; Hermine, Olivier; Kaveri, Srini V.

doi:10.1073/pnas.0402183101

Cited by 96 publications

(80 citation statements)

References 47 publications

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“…An example of the second case is the genetic disease X-linked agammaglobulinemia, in which a lack of DC maturation has been reported. Addition of natural IgG and of autoreactive antibodies to DC from these patients results in their maturation, as assessed by upregulation of major histocompatibility complex class II and costimulatory molecules (3). B. abortus resides in DC in vivo, and mouse DC are able to kill virB mutants (4,36).…”

Section: Discussionmentioning

confidence: 99%

Natural Antibody Contributes to Host Defense against an Attenuated Brucella abortus virB Mutant

Rolán¹,

Xavier

Santos

et al. 2009

Infect Immun

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Brucella abortus is an intracellular pathogen that persists within phagocytic cells of the reticuloendothelial system. To identify in vivo interactions between B. abortus and the host that lead to persistent infection, we studied the persistence of B. abortus and an isogenic virB mutant deficient in the VirB type IV secretion system (T4SS) in knockout mice. In contrast to control mice, mice lacking B cells (Igh6 ؊/؊ ) were permissive for infection with the attenuated virB mutant. To determine the basis for this phenotype, we characterized immune functions of Igh6 ؊/؊ mice in the context of B. abortus infection. Igh6 ؊/؊ mice had greater numbers of extracellular bacteria in the spleen and increased early expression of proinflammatory cytokines during B. abortus infection. Further, a virB mutant, despite its wild-type level of survival, failed to elicit microgranuloma formation in the spleens of Igh6 ؊/؊ mice, suggesting a requirement for the T4SS to elicit this pathological change. Passive transfer of immunoglobulin G from naïve mice restored the ability of Igh6 ؊/؊ mice to control the persistence of the virB mutant by a complement-independent mechanism. Further, adoptive transfer of CD11b ؉ cells from C57BL/6 mice to Igh6 ؊/؊ mice restored the ability of the knockout mice to limit the replication of the virB mutant in the spleen, suggesting that the Igh6 ؊/؊ mutation affects phagocyte function and that phagocyte function can be restored by natural antibody.Human brucellosis is a febrile disease resulting from the transmission of Brucella abortus, B. suis, B. melitensis, or B. canis from its respective zoonotic reservoir in cattle, swine, goats and sheep, or dogs (47). These pathogens are endemic in many areas of the world, including Central and South America, the Mediterranean, and Central Asia, and are responsible for an estimated 500,000 new brucellosis cases each year (1). In human brucellosis, as well as in the zoonotic reservoir species, bacteria may persist for long periods of time in the reticuloendothelial system (7). This aspect of infection can be modeled in the mouse, which has been used to identify and characterize the virulence factors involved in the systemic persistence of Brucella spp. (2,22).One essential virulence factor of the human pathogenic Brucella species is the type IV secretion system (T4SS) encoded by the virB locus on chromosome II (18,29,40). The T4SS of Brucella spp., similar to those of other bacterial pathogens, mediates the translocation of proteins into host cells; however, the functions of two newly identified B. abortus T4SS substrates, VceA and VceC, is not yet known (12,25,39,45,46). In cultured macrophages and dendritic cells (DC), the T4SS is essential for the intracellular replication and persistence of B. abortus (13,36,40). The T4SS mediates exclusion of late endosomal/lysosomal markers from the Brucella-containing vacuole and targeting of B. abortus to exit sites of the endoplasmic reticulum, where replication occurs (5, 6, 12, 41), suggesting that T4SS effectors are i...

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Section: Discussionmentioning

confidence: 99%

Natural Antibody Contributes to Host Defense against an Attenuated Brucella abortus virB Mutant

Rolán¹,

Xavier

Santos

et al. 2009

Infect Immun

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“…29 Previous studies have shown that IVIg can modulate diverse lymphoid and myeloid cell populations. 30,31 Thus, at therapeutic concentrations used in autoimmune diseases (0.15 mM), IVIg induces a downmodulation of monocyte-derived DC, which in turn fail to support T-cell proliferation. 30 We asked whether the mechanism whereby IVIg leads to an expansion of Treg is central to the protection against EAE or if it is a mere bystander effect.…”

Section: Discussionmentioning

confidence: 99%

Expansion of CD4+CD25+ regulatory T cells by intravenous immunoglobulin: a critical factor in controlling experimental autoimmune encephalomyelitis

Ephrem

Chamat

Miquel

et al. 2008

Blood

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254

217

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The clinical use of intravenous immunoglobulin (IVIg) based on its immunomodulatory and anti-inflammatory potential remains an ongoing challenge. Fc␥ receptor-mediated effects of IVIg, although well elucidated in certain pathologies, cannot entirely account for its proven benefit in several autoimmune disorders mediated by autoreactive T cells. In this study, we show that prophylactic infusion of IVIg prevents the devel- IntroductionNatural CD4 ϩ CD25 ϩ regulatory T cells (nTreg) expressing the lineage marker Foxp3 are the key players in controlling immune responses and in maintenance of T-cell homeostasis. 1,2 Therapeutic induction of the Treg represents a novel approach in the treatment of autoimmune pathology. 3,4 CD4 ϩ CD25 ϩ Foxp3 ϩ nTreg develop in thymus, in contrast to "adaptive" or "induced" Treg that develop in peripheral lymphoid tissues from CD4 ϩ conventional T cells (Tconv) and are frequently Foxp3 Ϫ . Although studies have highlighted the role of cytokines interleukin-2 (IL-2), transforming growth factor-␤ (TGF-␤), and IL-10 in Treg development, other factors or mechanisms crucial to Treg homeostasis are not elucidated. 5 Intravenous immunoglobulin (IVIg) is an established therapy for several immune disorders. [6][7][8][9] Several mutually nonexclusive mechanisms have been proposed to explain the beneficial effect of IVIg 7,8 ; however, the issue remains debated and an ongoing challenge. For instance, the Fc␥R-mediated effects of IVIg 10-12 cannot entirely account for its proven benefit in several peripheral and central demyelinating diseases such as GuillainBarré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), and relapsing-remitting multiple sclerosis (MS), which are primarily mediated by autoreactive T cells. 6,7,13,14 Because the T cells do not express Fc␥R, 15 the observed effects raise certain speculations, that is, if these effects could be attributed to a direct interaction of the variable region of the immunoglobulin (Ig) G molecules with the T cell or an indirect influence via other cell types such as dendritic cells (DC).During the induction phase of experimental autoimmune encephalomyelitis (EAE), myelin reactive proinflammatory CD4 ϩ T cells proliferate in the periphery, infiltrate the central nervous system (CNS) during the effector phase and, in concert with other inflammatory mediators, lead to demyelination characterized by a progressive paralysis. 16 Natural remission and recovery from relapse in EAE is associated with the recruitment or generation of Treg in the CNS. 17,18 We and others have shown that IVIg protects against EAE development only when administered prophylactically. 14,19 We reasoned that IVIg manifests its protective effect in EAE through an early modulation of autoreactive T cells, and therefore we investigated the regulatory mechanisms, particularly the effect of IVIg on regulatory T cells. Methods Animals, antigen, and tissue culture mediumWe purchased C57BL/6J mice (females, 6-8 weeks of age) from Charles River Laboratories (L'Arbresle, F...

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“…Studies on patients with common variable immunodeficiency (CVID), a heterogeneous disorder associated with low serum immunoglobulin concentrations, 18 suggest that their DCs are defective and that this, at least in part, is due to the low levels of serum antibodies. [19][20][21] Treatment with intravenous immunoglobulin (IVIg) to increase immunoglobulin levels has been beneficial in preventing infections in CVID patients, although the exact mechanism of IVIg treatment is not completely understood. 22 It has recently been suggested that the clinical effect of IVIg treatment in autoimmune disease involves the interaction of IVIg with activating Fc␥ receptors on DCs.…”

Section: Introductionmentioning

confidence: 99%

IgG regulates the CD1 expression profile and lipid antigen-presenting function in human dendritic cells via FcγRIIa

Smed‐Sörensen

Moll

Cheng

et al. 2008

Blood

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Natural antibodies sustain differentiation and maturation of human dendritic cells

Cited by 96 publications

References 47 publications

Natural Antibody Contributes to Host Defense against an Attenuated Brucella abortus virB Mutant

Natural Antibody Contributes to Host Defense against an Attenuated Brucella abortus virB Mutant

Expansion of CD4+CD25+ regulatory T cells by intravenous immunoglobulin: a critical factor in controlling experimental autoimmune encephalomyelitis

IgG regulates the CD1 expression profile and lipid antigen-presenting function in human dendritic cells via FcγRIIa

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