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Coordinated Regulation of Signaling Pathways during Macrophage Activation

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  • Author: Toby Lawrence1
  • Editor: Siamon Gordon2
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Inserm, CNRS, Marseille, France; 2: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0025-2015
  • Received 22 October 2015 Accepted 15 July 2016 Published 23 September 2016
  • Toby Lawrence, lawrence@ciml.univ-mrs.fr
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  • Abstract:

    The functional and phenotypic diversity of macrophages has long been appreciated, and it is now clear that it reflects a complex interplay between hard-wired differentiation pathways and instructive signals in specific tissues (Lawrence T, Natoli G. 2011, 750–761). Recent studies have begun to unravel the molecular basis for the integration of these intrinsic developmental pathways with extracellular signals from the tissue microenvironment that confer the distinct phenotypes of tissue-resident macrophages (Lavin Y et al. 2014. 1312–1326; Gosselin D et al. 2014. 1327–1340). Macrophage phenotype and function is particularly dynamic during inflammation or infection, as blood monocytes are recruited into tissues and differentiate into macrophages, and depending on the nature of the inflammatory stimulus, they may acquire distinct functional phenotypes (Xue J et al. 2014. 274–288; Murray PJ et al. 2014. 14–20). Furthermore, these functional activation states can be rapidly modified in response to a changing microenvironment. Here we will discuss several key signaling pathways that drive macrophage activation during the inflammatory response and discuss how these pathways are integrated to “fine-tune” macrophage phenotype and function.

  • Citation: Lawrence T. 2016. Coordinated Regulation of Signaling Pathways during Macrophage Activation. Microbiol Spectrum 4(5):MCHD-0025-2015. doi:10.1128/microbiolspec.MCHD-0025-2015.

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/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0025-2015
2016-09-23
2017-03-22

Abstract:

The functional and phenotypic diversity of macrophages has long been appreciated, and it is now clear that it reflects a complex interplay between hard-wired differentiation pathways and instructive signals in specific tissues (Lawrence T, Natoli G. 2011, 750–761). Recent studies have begun to unravel the molecular basis for the integration of these intrinsic developmental pathways with extracellular signals from the tissue microenvironment that confer the distinct phenotypes of tissue-resident macrophages (Lavin Y et al. 2014. 1312–1326; Gosselin D et al. 2014. 1327–1340). Macrophage phenotype and function is particularly dynamic during inflammation or infection, as blood monocytes are recruited into tissues and differentiate into macrophages, and depending on the nature of the inflammatory stimulus, they may acquire distinct functional phenotypes (Xue J et al. 2014. 274–288; Murray PJ et al. 2014. 14–20). Furthermore, these functional activation states can be rapidly modified in response to a changing microenvironment. Here we will discuss several key signaling pathways that drive macrophage activation during the inflammatory response and discuss how these pathways are integrated to “fine-tune” macrophage phenotype and function.

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FIGURE 1

Cross talk between signaling pathways in macrophages during encounters with microbial stimuli. Macrophages express a number of receptors that can recognize microbial patterns, including TLRs and phagocytic receptors. In addition, cytosolic detectors such as inflammasomes can respond to microbes that invade the cytoplasm of cells or escape the phagocytic compartment. TLRs directly trigger activation of NF-κB, through the IKK complex and MAPK pathways, to drive proinflammatory and anti-inflammatory cytokine expression. Endosomal TLR signaling also activates the TBK1 (TANK-binding kinase 1)-dependent expression of type I IFN (IFN-I) through triggering of IRF activation. Cytokines such as IFN-I, IL-6, and IL-10 can also trigger autocrine signaling through JAK/STAT activation, whereas other proinflammatory cytokines such as TNF-α and IL-1β activate IKK and MAPK pathways. There are a number of mechanisms for negative (red) and positive (green) cross talk between these signaling pathways in macrophages to fine-tune the magnitude and duration of their activation.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.MCHD-0025-2015
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