Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites

Tsou, Chia-Lin; Peters, Wendy; Si, Yue; Slaymaker, Sarah; Aslanian, Ara M.; Weisberg, Stuart P.; Mack, Matthias; Charo, Israel F.

doi:10.1172/jci29919

Cited by 950 publications

(955 citation statements)

References 35 publications

(39 reference statements)

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“…However, CCR2 and CXCR2 are important in mobilizing monocytes and neutrophils, respectively, from the bone marrow [7,8,35], which complicates deciphering the role of these chemokine receptors for subsequent recruitment to tissues. In support of this, Serbina and Pamer showed that CCR2 is not required for monocyte migration into infected spleen or inflamed peritoneum [7] while Tsou et al found that early, but not late phase, monocyte recruitment to the peritoneum is CCR2-dependent [9]. Thus, very refined studies are required to directly assess the role of CCR2 for migration from blood into inflamed tissues during oral Salmonella infection.…”

Section: Discussionmentioning

confidence: 99%

“…39: 3019-3030 DOI 10.1002 Immunity to infection 3019 marrow into the blood during steady state and infection [7][8][9][10]. They are also central for monocyte and neutrophil recruitment and host survival during infections [9,[11][12][13][14][15][16]. Despite the undisputed role of chemokine receptors and their ligands in ensuring survival to infection, it is difficult to assess the role of individual chemokines in phagocyte recruitment, particularly in the complex environment of bacterial-infected tissues.…”

Section: Introductionmentioning

confidence: 99%

“…An array of chemokines is induced by inflammation and recruits monocytes, neutrophils and other cells to sites of infection. The chemokine receptors CCR2 and CXCR2 are required for monocytes and neutrophils, respectively, to egress from the bone marrow into the blood during steady state and infection [7][8][9][10]. They are also central for monocyte and neutrophil recruitment and host survival during infections [9,[11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Monocyte and neutrophil recruitment during oral Salmonella infection is driven by MyD88‐derived chemokines

Rydström

Wick

2009

Eur J Immunol

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Oral Salmonella infection recruits phagocytes to Peyer's patches (PP) and MLN. The chemokines induced in infected PP and MLN, the cellular sources during infection and the TLR signaling pathways involved in vivo are not known. Here, we show that CCL2, CXCL9 and CXCL2 mRNA are up-regulated in PP and MLN coincident with the first arrival of monocytes and neutrophils. Laser capture microdissection microscopy revealed that chemokine mRNA up-regulation was differently distributed in PP. Despite this, recruited monocytes and neutrophils formed inflammatory cell clusters throughout PP. Monocytes and neutrophils purified from infected mice preferentially produced CXCL2 and small amounts of CCL2, and neutrophils from infected mice migrated towards CXCL2 and CCL3. Furthermore, phagocyte recruitment to PP and MLN was intact in mice lacking TLR4 alone and when signaling through TLR4 and TLR5 was simultaneously absent; however, recruitment was compromised in MyD88 À/À and more so in MyD88 À/À TLR4 À/À double knockout mice. Phagocyte release into the blood, however, was only marginally reduced in MyD88 À/À TLR4 À/À mice. Defective phagocyte recruitment to PP and MLN of MyD88 À/À TLR4 À/À mice was paralleled by low chemokine induction. These data provide insight into the chemokines and TLR signaling pathways that orchestrate the early phagocyte response to oral Salmonella infection.Key words: Chemokine . Monocyte . Salmonella . TLR IntroductionMonocytes and neutrophils are critical in the first line of defense against bacteria. They develop in the bone marrow, are released into the circulation and enter tissues in response to infection. Murine monocytes in the blood are a heterogeneous population and have been divided into two main subsets based on whether they are present in steady state or recruited under inflammatory conditions [1]. Inflammatory Gr-1 hi CCR2 hi CX 3 CR1 low monocytes, which have also been called TipDC upon entering a tissue, are a source of molecules important in controlling bacterial infection, particularly iNOS and TNF-a [2][3][4].Salmonella enterica serovar Typhimurium (S. typhimurium) is a Gram-negative facultative intracellular bacterium that infects via the oral route. Orally acquired Salmonella exits the gut lumen primarily by crossing the follicle-associated epithelium overlying Peyer's patches (PP) via M cells (reviewed in [5]). The bacteria are then further spread to the MLN, most likely by DC, and to the spleen and liver via the blood [5,6]. After oral infection with S. typhimurium, neutrophils and Gr-1 hi CCR2 hi inflammatory monocytes accumulate in PP and MLN, the first organs encountering the bacteria, beginning 2-3 days after infection [3].Chemokines are the main mediators involved in the recruitment and migration of leukocytes to and within tissues. An array of chemokines is induced by inflammation and recruits monocytes, neutrophils and other cells to sites of infection. The chemokine receptors CCR2 and CXCR2 are required for monocytes and neutrophils, respectively, to egress from the bone ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Monocyte and neutrophil recruitment during oral Salmonella infection is driven by MyD88‐derived chemokines

Rydström

Wick

2009

Eur J Immunol

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“…While monocytes are also formed in the liver and spleen [70][71][72], the view that monocytes are derived from the bone marrow has been established since the early 1960s and still dominates [73]. The monocytes produced from the bone marrow exit to the circulatory system in a C-C chemokine receptor 2 (CCR2)-dependent manner and enter tissues to give rise to tissue macrophages [74]. Circulating monocytes possess 2 distinct phenotypes with unique functional properties in human and mice.…”

Section: Monocytes and Monocyte-derived Macrophagesmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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“…Leur devenir dépend de leur phénotype, d'une part, et du microenvironnement dans lequel elles vont se diffé-rencier en macrophages, d'autre part. Chez la souris, les monocytes Gr1 + Ly-6C high , équivalents des monocytes classiques CD14 + CD16 -chez l'homme, seraient les précurseurs des macrophages pro-inflammatoires du tissu adipeux [18,19]. Chez l'homme, des premiers travaux ont révélé que les cellules mononucléées circulantes expriment un statut pro-inflammatoire chez les sujets obèses [20].…”

Section: D'où Viennent Les Macrophages Du Tissu Adipeux ?unclassified