JAK-ing into M1/M2 Polarization SteErs Salmonella-Containing Macrophages Away from Immune Attack to Promote Bacterial Persistence

Brodsky, Igor E.

doi:10.1016/j.chom.2019.12.007

Cited by 14 publications

(10 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STAT3 phosphorylation in Y705 is required for dimerization and transcriptional activation [32]. In agreement with our data, this phosphorylation in STAT3 was shown to polarize macrophages towards an M2 phenotype in models of salmonella infection, myocardial infraction and cancer [33][34][35]. Moreover, our proteomic data indicated that LIPA was up-regulated specifically in TAMs.…”

Section: Discussionsupporting

confidence: 90%

A Proteomic Atlas of Lineage and Cancer-Polarized Expression Modules in Myeloid Cells Modeling Immunosuppressive Tumor-Infiltrating Subsets

Blanco

Ibáñez-Vea

Hernández

et al. 2021

JPM

View full text Add to dashboard Cite

Monocytic and granulocytic myeloid-derived suppressor cells together with tumor-infiltrating macrophages constitute the main tumor-infiltrating immunosuppressive myeloid populations. Due to the phenotypic resemblance to conventional myeloid cells, their identification and purification from within the tumors is technically difficult and makes their study a challenge. We differentiated myeloid cells modeling the three main tumor-infiltrating types together with uncommitted macrophages, using ex vivo differentiation methods resembling the tumor microenvironment. The phenotype and proteome of these cells was compared to identify linage-dependent relationships and cancer-specific interactome expression modules. The relationships between monocytic MDSCs and TAMs, monocytic MDSCs and granulocytic MDSCs, and hierarchical relationships of expression networks and transcription factors due to lineage and cancer polarization were mapped. Highly purified immunosuppressive myeloid cell populations that model tumor-infiltrating counterparts were systematically analyzed by quantitative proteomics. Full functional interactome maps have been generated to characterize at high resolution the relationships between the three main myeloid tumor-infiltrating cell types. Our data highlights the biological processes related to each cell type, and uncover novel shared and differential molecular targets. Moreover, the high numbers and fidelity of ex vivo-generated subsets to their natural tumor-shaped counterparts enable their use for validation of new treatments in high-throughput experiments.

show abstract

Section: Discussionsupporting

confidence: 90%

A Proteomic Atlas of Lineage and Cancer-Polarized Expression Modules in Myeloid Cells Modeling Immunosuppressive Tumor-Infiltrating Subsets

Blanco

Ibáñez-Vea

Hernández

et al. 2021

JPM

View full text Add to dashboard Cite

show abstract

“…In addition, the SteE effector protein increased the polarization of M2 macrophages in granulomas ( 11 ). Recently, Brodsky et al obtained similar results that SteE protects the intracellular Salmonella from TNF-mediated granuloma clearance and hypothesized that SteE can polarize M2 macrophages ( 27 ). Furthermore, the steE -driven M2 granuloma macrophages polarization reduced iNOS mRNA expression compared to M1 granuloma macrophages, but the mRNA levels of IL-4 were significantly high ( 11 , 29 ).…”

Section: Discussionmentioning

confidence: 92%

“…Pullorum in HD-11 cells. Recent studies have evaluated the mechanisms underlying steE -mediated regulation of macrophage polarization and have provided insights into chronic infection with Salmonella ( 26 , 27 ). Furthermore, SPI-2 effector mutants ( ssaV and steE ) in S .…”

Section: Discussionmentioning

confidence: 99%

SteE Enhances the Virulence of Salmonella Pullorum in Chickens by Regulating the Inflammation Response

Liu

Wang

et al. 2022

Front. Vet. Sci.

View full text Add to dashboard Cite

Salmonella enterica serovar Pullorum (S. Pullorum) is a host-specific pathogen, which causes acute gastroenteritis with high mortality in poultry. However, the association between steE, encoded by type III secretion system 2, and Salmonella virulence is not well-understood. To elucidate the functions of steE in S. Pullorum, ΔsteE strain was constructed using the λ-Red recombination technology. Compared to that in the wild-type, the deletion of steE in S. Pullorum reduced bacterial invasion, proliferation, and late apoptosis in the infected HD-11 cells. In addition, we analyzed the mRNA expression levels of effector genes and cytokines by qRT-PCR. SteE was associated with the regulation of various effector genes and inflammatory cytokines in HD-11 cells during S. Pullorum infection. The wild-type effector steE promoted the expression of anti-inflammatory cytokines (IL-4 and IL-10) and reduced that of pro-inflammatory cytokines (IL-1β, IL-6, and IL-12) compared to that in the ΔsteE-infected HD-11 cells and chicken spleens. Results from the chicken infection model showed that the deletion of steE resulted in significantly decreased colonization and long-term survival of the bacteria and alleviated pathological lesions compared to those in the wild-type. Further, steE increased the virulence of S. Pullorum in chickens by regulating the expression of inflammatory cytokines. Our findings provide insights into the persistent infection and autoimmunity associated with steE in S. Pullorum.

show abstract

“…Cytokines such as interferon (IFNγ) transform resting macrophages into classically activated macrophages, commonly known as the M1 phenotype. M1 macrophages amplify the cellular antigen presenting capacity, complement mediated phagocytosis, and secrete pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL-1, 6), STAT1, STAT3, IRF4, NF-κB, CIITA, CD80, CD86, and reactive nitrogen, which leads to a strong bactericidal and tumoricidal activity ( Brodsky, 2020 ; Feske et al., 2015 ; Han et al., 2017 ). Similarly, IL-4, which is mainly produced by Th2 cells, transforms naive macrophages into alternatively activated macrophages, or the M2 phenotype, which express molecules including Arginase1 (Arg1), chitinase 3, OCS1, PPARγ, STAT6, GATA3, c-MYC, HIF-1α, LXR, CD163, CD36, TGFβ, IL-10, and CD206.…”

Section: Introductionmentioning

confidence: 99%

Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics

et al. 2021

View full text Add to dashboard Cite

Summary Transformation of naive macrophages into classically (M1) or alternatively (M2) activated macrophages regulates the inflammatory response. Here, we identified that distinct Ca 2+ entry channels determine the IFNγ-induced M1 or IL-4-induced M2 transition. Naive or M2 macrophages exhibit a robust Ca 2+ entry that was dependent on Orai1 channels, whereas the M1 phenotype showed a non-selective TRPC1 current. Blockade of Ca 2+ entry suppresses pNF-κB/pJNK/STAT1 or STAT6 signaling events and consequently lowers cytokine production that is essential for M1 or M2 functions. Of importance, LPS stimulation shifted M2 cells from Orai1 toward TRPC1-mediated Ca 2+ entry and TRPC1 −/− mice exhibited transcriptional changes that suppress pro-inflammatory cytokines. In contrast, Orai1 −/− macrophages showed a decrease in anti-inflammatory cytokines and exhibited a suppression of mitochondrial oxygen consumption rate and inhibited mitochondrial shape transition specifically in the M2 cells. Finally, alterations in TRPC1 or Orai1 expression determine macrophage polarization suggesting a distinct role of Ca 2+ channels in modulating macrophage transformation.

show abstract

JAK-ing into M1/M2 Polarization SteErs Salmonella-Containing Macrophages Away from Immune Attack to Promote Bacterial Persistence

Cited by 14 publications

References 13 publications

A Proteomic Atlas of Lineage and Cancer-Polarized Expression Modules in Myeloid Cells Modeling Immunosuppressive Tumor-Infiltrating Subsets

A Proteomic Atlas of Lineage and Cancer-Polarized Expression Modules in Myeloid Cells Modeling Immunosuppressive Tumor-Infiltrating Subsets

SteE Enhances the Virulence of Salmonella Pullorum in Chickens by Regulating the Inflammation Response

Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics

Contact Info

Product

Resources

About