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CD169(+) macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes.

ABSTRACT: Invariant natural killer T cells (iNKT cells) are involved in the host defense against microbial infection. Although it is known that iNKT cells recognize glycolipids presented by CD1d, how and where they encounter antigen in vivo remains unclear. Here we used multiphoton microscopy to visualize the dynamics and activation of iNKT cells in lymph nodes. After antigen administration, iNKT cells became confined in a CD1d-dependent manner in close proximity to subcapsular sinus CD169(+) macrophages. These macrophages retained, internalized and presented lipid antigen and were required for iNKT cell activation, cytokine production and population expansion. Thus, CD169(+) macrophages can act as true antigen-presenting cells controlling early iNKT cell activation and favoring the fast initiation of immune responses.

SUBMITTER: Barral P

PROVIDER: S-EPMC2923071 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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CD169(+) macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes.

Barral Patricia P Polzella Paolo P Bruckbauer Andreas A van Rooijen Nico N Besra Gurdyal S GS Cerundolo Vincenzo V Batista Facundo D FD

Nature immunology 20100314 4

Invariant natural killer T cells (iNKT cells) are involved in the host defense against microbial infection. Although it is known that iNKT cells recognize glycolipids presented by CD1d, how and where they encounter antigen in vivo remains unclear. Here we used multiphoton microscopy to visualize the dynamics and activation of iNKT cells in lymph nodes. After antigen administration, iNKT cells became confined in a CD1d-dependent manner in close proximity to subcapsular sinus CD169(+) macrophages. ...[more]

PMID: 20228797

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CD169-positive sinus macrophages in the lymph nodes determine bladder cancer prognosis.

Project description:CD169+ macrophages are suggested to play a pivotal role in establishing anti-tumor immunity. They capture dead tumor cell-associated antigens and transfer their information to lymphocsytes, including CD8+ T cells, which is important for successful tumor suppression. This study aimed to determine the prognostic significance of CD169+ macrophages residing in the tumor-draining lymph nodes from cases of bladder cancer. In this retrospective study, 44 bladder cancer patients who received radical cystectomy were examined. The abundance of CD169+ macrophages in the regional lymph nodes and the number of CD8+ T cells in the primary tumor were investigated by immunohistochemistry. A CD169 score was calculated based on the intensity of CD169 staining and the proportion of CD169+ macrophages, and the scores were compared to the patients' clinicopathological parameters. A high CD169 score was significantly associated with low T stage and with a high number of CD8+ T cells infiltrating into the tumor. The group with high CD169 expression had significantly longer cancer-specific survival than the group with low CD169 expression (5-year cancer-specific survival rate: 83.3% vs 31.3%). In a multivariate analysis, the CD169 score was identified as a strong and independent favorable prognostic factor for cancer-specific survival. Our findings suggest that CD169+ macrophages in the lymph nodes enhance anti-tumor immunity by expanding CD8+ T cells in bladder cancer. The CD169 score may serve as a novel marker for the evaluation of bladder cancer prognosis.

| S-EPMC5980134 | biostudies-literature

CD169-positive macrophages in regional lymph nodes are associated with a favorable prognosis in patients with colorectal carcinoma.

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2023-02-16 | GSE214060 | GEO

Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma.

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CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling.

Project description:CD169+ macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169+ macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTβ) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTβR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTβR revealed that both receptors contribute equally to LN CD169+ macrophage differentiation. In the spleen, the Cd169-directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD8+ T cells. Taken together, the data provide evidence that CD169+ macrophage differentiation in LN and spleen requires dual signals from LTβR and RANK with implications for the immune response.

| S-EPMC8784161 | biostudies-literature

Significance of para-esophageal lymph nodes in food or aeroallergen-induced iNKT cell-mediated experimental eosinophilic esophagitis.

Project description:Eosinophilic esophagitis (EoE) is a recently recognized inflammatory disorder driven by food hypersensitivity; however, the specific foods and mechanisms involved are unclear. In patients with EoE, we have found that hypersensitivities to corn and peanuts are the most common. Accordingly, we sensitized and exposed mice either intranasally or intragastrically with corn or peanut extract or saline. Esophageal eosinophilia, the genes of eosinophil-directed cytokines, and allergen-induced antibodies were examined in mice challenged with corn or peanut extract or saline. A high number of esophageal lamina propria eosinophils as well as eosinophilic microabscesses, intraepithelial eosinophils, extracellular eosinophilic granules, thickened and disrupted epithelial mucosa, and mast cell hyperplasia were observed in the esophagus of peanut or corn allergen-challenged mice. Mechanistic analysis indicated that para-esophageal lymph nodes might be critical in the trafficking of eosinophils to the esophagus and in EoE association to airway eosinophilia. Furthermore, experimentation with gene-targeted mice revealed that peanut allergen-induced EoE was dependent on eotaxin and invariant natural killer T (iNKT) cells, as CD1d and eotaxin-1/2 gene-deficient mice were protected from disease induction. Thus we provide evidence that para-esophageal lymph nodes are involved in food- or aeroallergen-induced eosinophilia and patchy EoE pathogenesis, likely a mechanism dependent on eotaxins and iNKT cells.

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CD169 Expressing Macrophage, a Key Subset in Mesenteric Lymph Nodes Promotes Mucosal Inflammation in Dextran Sulfate Sodium-Induced Colitis.

Project description:Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis is a relapsing-remitting illness. Patients with long-standing extensive colitis are easy to develop colorectal cancer (CRC). The increasing incidence of IBD and a substantial increase in the risk of CRC make the necessity to pay more attention on the regulation of inflammation especially by specific macrophages subset. The present study reported that a key subset of sinus macrophage expressing CD169 in mesenteric lymph nodes (mLNs) played an essential role in promoting mucosal inflammation. The results revealed that the subset expressing CD169 in mLNs increased significantly during the dextran sulfate sodium (DSS)-induced colitis. The colitic symptoms were alleviated in CD169-diphtheria toxin receptor (DTR) mice at least partially due to the deletion of CD169+ macrophages in mLNs. In addition, the levels of inflammatory cytokines as well as the percentage of Th17?cells in mLNs from CD169-DTR mice were much lower than those from WT mice with DSS-induced colitis. Further experiment in vitro demonstrated that the supernatant from whole cells of mLNs or colon tissues could promote the production of inflammatory factors by mLN cells or colon tissues from CD169-DTR mice. These results could be explained by the cell sorting result that CD11b+CD169+ macrophages expressed higher level of inflammatory factors directly. All these data indicated that CD169+ sinus macrophage in mLNs played an essential role on regulating mucosal inflammation.

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Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation.

Project description:Invariant natural killer T (iNKT) cells induce a protective immune response triggered by foreign glycolipid antigens bound to CD1d on antigen-presenting cells (APCs). A limitation of using glycolipid antigens to stimulate immune responses in human patients has been the inability to target them to the most effective APCs. Recent studies have implicated phagocytic CD169(+) macrophages as major APCs in lymph nodes for priming iNKT cells in mice immunized with glycolipid antigen in particulate form. CD169 is known as sialoadhesin (Sn), a macrophage-specific adhesion and endocytic receptor of the siglec family that recognizes sialic acid containing glycans as ligands. We have recently developed liposomes decorated with glycan ligands for CD169/Sn suitable for targeted delivery to macrophages via CD169/Sn-mediated endocytosis. Here we show that targeted delivery of a lipid antigen to CD169(+) macrophages in vivo results in robust iNKT cell activation in liver and spleen using nanogram amounts of antigen. Activation of iNKT cells is abrogated in Cd169(-/-) mice and is macrophage-dependent, demonstrating that targeting CD169(+) macrophages is sufficient for systemic activation of iNKT cells. When pulsed with targeted liposomes, human monocyte-derived dendritic cells expressing CD169/Sn activated human iNKT cells, demonstrating the conservation of the CD169/Sn endocytic pathway capable of presenting lipid antigens to iNKT cells.

| S-EPMC3651435 | biostudies-literature

Natural Killer Cells Mediate Protection against Yersinia pseudotuberculosis in the Mesenteric Lymph Nodes.

Project description:Natural killer cells play a crucial role in the initial defense against bacterial pathogens. The crosstalk between host cells infected with intracellular pathogens and NK cells has been studied intensively, but not much attention has been given to characterize the role of NK cells in the response to extracellular bacterial pathogens such as yersiniae. In this study we used antibody-mediated NK cell depletion to address the importance of this immune cell type in controlling a Y. pseudotuberculosis infection. Analysis of the bacterial counts was used to follow the infection and flow cytometry was performed to characterize the composition and dynamic of immune cells. Depletion of NK cells led to higher bacterial loads within the mesenteric lymph nodes. We further show that in particular CD11b+ CD27+ NK cells which express higher levels of the activation marker CD69 increase within the mesenteric lymph nodes during a Y. pseudotuberculosis infection. Moreover, in response to the activation NK cells secrete higher levels of IFNy, which in turn triggers the production of the proinflammatory cytokine TNFα. These results suggest, that NK cells aid in the clearance of Y. pseudotuberculosis infections mainly by triggering the expression of proinflammatory cytokines manipulating the host immune response.

| S-EPMC4546584 | biostudies-literature

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