Triggering of protease-activated receptors (PARs) induces alternative M2 macrophage polarization with impaired plasticity

García-González, Gerardo; Sánchez-González, Alejandro; Hernández-Bello, Romel; González, Gloria M.; Franco‐Molina, Moises Armides; Coronado‐Cerda, Erika Evangelina; Palma-Nicolás, José Prisco

doi:10.1016/j.molimm.2019.08.004

Cited by 17 publications

(15 citation statements)

References 35 publications

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“…In this study this plasticity was modulated by transcription factors produced by EES, and by the EES itself, at 24 and 48 hr after phagocytosis. CD206 has been shown to recognize the surface carbohydrates of pathogens and be triggered by proteases produced by B. subtilis (Corvey et al, 2003;García-González et al, 2019;Stahl and Ezekowitz, 1998). Thus, CD206 marker expression is complex and may be increased by nonspecific factors.…”

Section: Discussionmentioning

confidence: 99%

Engineered endosymbionts capable of directing mammalian cell gene expression

Madsen

Makela

Greeson

et al. 2021

Preprint

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Modular methods for directing mammalian gene expression would enable advances in tissue regeneration, enhance cell-based therapeutics and improve modulation of immune responses. To address this challenge, engineered endosymbionts (EES) that escape endosomal destruction, reside in the cytoplasm of mammalian cells, and secrete proteins that are transported to the nucleus to control host cell gene expression were developed. Microscopy confirmed that EES escape phagosomes, replicate within the cytoplasm, and can secrete reporter proteins into the cytoplasm that were then transported to the nucleus. Synthetic operons encoding the mammalian transcription factors, Stat-1 and Klf6 or Klf4 and Gata-3 were recombined into the EES genome. Using controlled induction, these EES were shown to direct gene expression in J774A.1 macrophage/monocyte cells and modulate the host cell fates. Expressing mammalian transcription factors from engineered intracellular bacteria as endosymbionts comprises a new tool for directing host cell gene expression for therapeutic and research purposes.

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Section: Discussionmentioning

confidence: 99%

Engineered endosymbionts capable of directing mammalian cell gene expression

Madsen

Makela

Greeson

et al. 2021

Preprint

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“…However, conjoint activation of PAR2 and TLR4 in peritoneal M polarized them toward the M2 phenotype, since PAR2 peptide suppressed the LPSmediated increase in M1 cytokines (TNFα, IL-6 and IL-12p40) (174). Similarly, other studies have shown that PAR2 null primary macrophages secreted less IL-4/IL-13 in response to LPS as compared to wild-type macrophages, and PAR2 activation was associated with greater M2 cytokine expression after LPS exposure (174,176).…”

Section: Role In Macrophage Polarizationmentioning

confidence: 92%

Macrophage TLR4 and PAR2 Signaling: Role in Regulating Vascular Inflammatory Injury and Repair

et al. 2020

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Macrophages play a central role in dictating the tissue response to infection and orchestrating subsequent repair of the damage. In this context, macrophages residing in the lungs continuously sense and discriminate among a wide range of insults to initiate the immune responses important to host-defense. Inflammatory tissue injury also leads to activation of proteases, and thereby the coagulation pathway, to optimize injury and repair post-infection. However, long-lasting inflammatory triggers from macrophages can impair the lung's ability to recover from severe injury, leading to increased lung vascular permeability and neutrophilic injury, hallmarks of Acute Lung Injury (ALI). In this review, we discuss the roles of toll-like receptor 4 (TLR4) and protease activating receptor 2 (PAR2) expressed on the macrophage cell-surface in regulating lung vascular inflammatory signaling.

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“…Protease activate receptors (PAR1/2)‐activated monocytes when co‐culture with T/B lymphocytes stimulated with M. tb antigen, CFP, result in IL‐4 secreting M2 macrophage. These macrophages also showed decreased M1 cytokine IFN‐ɣ and IL‐12 with the reduced capability of re‐differentiation into the M1 macrophages [51]. Hence, the above observation suggests that cytokines not only polarize macrophages but also can repolarize fully differentiated macrophages.…”

Section: Mycobacterial‐mediated Macrophage Reprogrammingmentioning

confidence: 99%

Macrophage plasticity as a therapeutic target in tuberculosis

Arish

Naz

2022

Eur J Immunol

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The macrophages contribute to host defense against intracellular pathogens such as mycobacteria. Mycobacteria interact with macrophages altering their polarization state, which propagates establishment of infection. Thus, molecular macrophage properties in mycobacterial infections are critical both for understanding the biology of the infections as well as identifying therapeutic targets. Here, we review recent advances in the understanding how altered macrophage polarization in mycobacterial infections may lead to the design of targeted therapies that may reprogram these macrophages for enhanced mycobactericidal function.

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Triggering of protease-activated receptors (PARs) induces alternative M2 macrophage polarization with impaired plasticity

Cited by 17 publications

References 35 publications

Engineered endosymbionts capable of directing mammalian cell gene expression

Engineered endosymbionts capable of directing mammalian cell gene expression

Macrophage TLR4 and PAR2 Signaling: Role in Regulating Vascular Inflammatory Injury and Repair

Macrophage plasticity as a therapeutic target in tuberculosis

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