NK Cell-Derived Interferon-γ Orchestrates Cellular Dynamics and the Differentiation of Monocytes into Dendritic Cells at the Site of Infection

Goldszmid, Romina S.; Caspar, Patricia; Rivollier, Aymeric; White, Steve; Dzutsev, Amiran; Hieny, Sara; Kelsall, Brian L.; Trinchieri, Giorgio; Sher, Alan

doi:10.1016/j.immuni.2012.03.026

Cited by 253 publications

(273 citation statements)

References 50 publications

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“…The differentiation of monocytes into DCs is mostly observed under inflammatory conditions (25,26), and consistent with this view, it has been shown that inflammation triggers the massive recruitment of monocytes into the vaginal epithelium and their subsequent differentiation into DCs (20). Thus, we speculate that the deposition of semen in the female genital mucosa might be able not only to induce the local recruitment of monocytes (7,20), but also to modulate the differentiation profile of monocyte-derived DCs.…”

supporting

confidence: 82%

“…Monocytes represent the most important reservoir of myeloid precursors for the renewal of tissue macrophages and DCs (25,26). The differentiation of monocytes into DCs is mostly observed under inflammatory conditions (25,26), and consistent with this view, it has been shown that inflammation triggers the massive recruitment of monocytes into the vaginal epithelium and their subsequent differentiation into DCs (20).…”

mentioning

confidence: 72%

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Semen Promotes the Differentiation of Tolerogenic Dendritic Cells

Lenicov

Rodrígues

Sabatté

et al. 2012

The Journal of Immunology

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Seminal plasma is not just a carrier for spermatozoa. It contains high concentrations of cytokines, chemokines, and other biological compounds that are able to exert potent effects on the immune system of the receptive partner. Previous studies have shown that semen induces an acute inflammatory response at the female genital mucosa after coitus. Moreover, it induces regulatory mechanisms that allow the fetus (a semiallograft) to grow and develop in the uterus. The mechanisms underlying these regulatory mechanisms, however, are poorly understood. In this study, we show that seminal plasma redirects the differentiation of human dendritic cells (DCs) toward a regulatory profile. DCs differentiated from human monocytes in the presence of high dilutions of seminal plasma did not express CD1a but showed high levels of CD14. They were unable to develop a fully mature phenotype in response to LPS, TNF-α, CD40L, Pam2CSK4 (TLR2/6 agonist), or Pam3CSK4 (TLR1/2 agonist). Upon activation, they produced low amounts of the inflammatory cytokines IL-12p70, IL-1β, TNF-α, and IL-6, but expressed a high ability to produce IL-10 and TGF-β. Inhibition of the PG receptors E-prostanoid receptors 2 and 4 prevented the tolerogenic effect induced by seminal plasma on the phenotype and function of DCs, suggesting that E-series PGs play a major role. By promoting a tolerogenic profile in DCs, seminal plasma might favor fertility, but might also compromise the capacity of the receptive partner to mount an effective immune response against sexually transmitted pathogens.

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supporting

confidence: 82%

mentioning

confidence: 72%

Semen Promotes the Differentiation of Tolerogenic Dendritic Cells

Lenicov

Rodrígues

Sabatté

et al. 2012

The Journal of Immunology

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“…23 Functional analysis further demonstrated that expanded CD56 bri NK cells retained IFNg production, which is known to promote antimicrobial immunity through the maturation of dendritic cells and the induction of Th1 responses. 24,25 Our previous study also found that rapid reconstitution of CD56 bri NK cells was associated with a lower TRM post-transplantation. 21 Therefore, the IL-2-induced expansion of CD56 bri NK cells could not only decrease the incidence of moderate-to-severe cGVHD but also enhance the anti-infection capacity of patients, which could explain its contribution to the lower incidence of NRM in the IL-2 arm.…”

Section: Discussionmentioning

confidence: 88%

Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study

Zhao

Wang

et al. 2016

OncoImmunology

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Leukemia relapse and chronic graft-versus-host disease (cGVHD) are still major obstacles of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The numbers and activity of natural killer (NK) and Tregulatory cells can be increased post-transplantation by exposure to interleukin-2 (IL-2). We tested whether administering low-dose IL-2 would decrease leukemia relapse while reducing cGVHD after allotransplantation. This controlled, open-label randomized trial included 90 recipients of allotransplants. Subjects were randomized in a 1:1 ratio to either receive or not receive low-dose IL-2 during the early post-transplantation period. Patients in the IL-2 arm received a subcutaneous injection of low-dose IL-2 (1£10 6 U/d) on day 60 after allo-HSCT. IL-2 was administered daily for 14 d followed by a 14-d hiatus. The primary endpoint was the cumulative incidence of leukemia relapse (CIR). Three-year CIRs for the IL-2 arm and control arm were 23% (range 16-30%) and 11% (range 6-15%; p D 0.20), respectively. Minimal residual disease-positive (MRDC) tests were more common in the IL-2 arm compared to the control arm (36% [range 29-44%] vs. 15% [range 10-20%], p D 0.03). The cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) was lower in the IL-2 arm compared to the control arm (33% [range 26-39%] vs. 57% [range 49-64%), p D 0.02). Therefore, the 3-y GVHD-free and GVHD progression-free survival (GPFS) rates were significantly higher in the IL-2 arm compared to the control arm (47% [range 39-55%] vs. 31% [range 25-38%], p D 0.048). Blood Tregs, NK cells, and NK-cell cytotoxicity were increased in subjects in the IL-2 arm between 3 mo and 6 mo post-transplantation. Administration of low-dose IL-2 during the immediate post-transplantation period was associated with a higher GPFS but did not decrease the CIR.

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“…The differentiation of monocytes into DCs was thought to be dependent on GM-CSF, because GM-CSF can induce DC differentiation from monocytes in vitro and is elevated during inflammation in vivo (39). However, recent data in GM-CSFR-deficient mice suggest that GM-CSF is dispensable (40), whereas IFN-g produced by NK cells can drive monocyte differentiation into DCs (41). In our study, serum GM-CSF levels were variable, and elevated serum IFN-g and production of IFN-g by NK cells correlated well with increased numbers of monocyte-derived DCs in dLNs and a successful response to immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Increased Numbers of Monocyte-Derived Dendritic Cells during Successful Tumor Immunotherapy with Immune-Activating Agents

Kühn

Hyde

Yang

et al. 2013

The Journal of Immunology

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Local treatment with selected TLR ligands or bacteria such as bacillus Calmette–Guérin increases antitumor immune responses and delays tumor growth. It is thought that these treatments may act by activating tumor-associated dendritic cells (DCs), thereby supporting the induction of antitumor immune responses. However, common parameters of successful immune activation have not been identified. We used mouse models to compare treatments with different immune-activating agents for the ability to delay tumor growth, improve priming of tumor-specific T cells, and induce early cytokine production and DC activation. Treatment with polyinosinic-polycytidylic acid or a combination of monosodium urate crystals and Mycobacterium smegmatis was effective at delaying the growth of s.c. B16 melanomas, orthotopic 4T1 mammary carcinomas, and reducing 4T1 lung metastases. In contrast, LPS, monosodium urate crystals, or M. smegmatis alone had no activity. Effective treatments required both NK1.1+ and CD8+ cells, and resulted in increased T cell priming and the infiltration of NK cells and CD8+ T cells in tumors. Unexpectedly, both effective and ineffective treatments increased DC numbers and the expression of costimulatory molecules in the tumor-draining lymph node. However, only effective treatments induced the rapid appearance of a population of monocyte-derived DCs in the draining lymph node, early release of IL-12p70 and IFN-γ, and low IL-10 in the serum. These results suggest that the activation of existing DC subsets is not sufficient for the induction of antitumor immune responses, whereas early induction of Th1 cytokines and monocyte-derived DCs are features of successful activation of antitumor immunity.

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NK Cell-Derived Interferon-γ Orchestrates Cellular Dynamics and the Differentiation of Monocytes into Dendritic Cells at the Site of Infection

Cited by 253 publications

References 50 publications

Semen Promotes the Differentiation of Tolerogenic Dendritic Cells

Semen Promotes the Differentiation of Tolerogenic Dendritic Cells

Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study

Increased Numbers of Monocyte-Derived Dendritic Cells during Successful Tumor Immunotherapy with Immune-Activating Agents

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