Phagosomal Acidification Prevents Macrophage Inflammatory Cytokine Production to Malaria, and Dendritic Cells Are the Major Source at the Early Stages of Infection

Wu, Xianzhu; Gowda, Nagaraj; Gowda, X. D.Channe

doi:10.1074/jbc.m115.671065

Cited by 28 publications

(39 citation statements)

References 53 publications

(86 reference statements)

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“…Isolation of Mouse Parasites-Preparation of iRBCs was performed based on earlier published protocols (36). In brief, blood from PbA-infected mice was diluted with PBS (pH 7.4) and centrifuged on Lymphoprep cushions at room temperature for 15 min.…”

Section: Methodsmentioning

confidence: 99%

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Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism

Alferink

Specht²,

Arends

et al. 2016

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

“…4F). We further investigated whether increased numbers of CD11b ϩ cells in the Cnr2 Ϫ/Ϫ spleen also comprise macrophages by utilizing previously published gating strategies (36) (Fig. 4G) (Fig.…”

Section: Enhanced Numbers Of Macrophages and Neutrophils In The Spleementioning

confidence: 99%

Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism

Alferink

Specht²,

Arends

et al. 2016

Journal of Biological Chemistry

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“…PbA and Py IRBCs were purified to ~80% parasitemia as described (10,21,35). Pf merozoites were purified to ~95% parasitemia by centrifugation on 30% percoll (10,21).…”

Section: Mice and Malaria Infection-tlr2mentioning

confidence: 99%

“…Preparation of DC, basophils, and mast cells-FL-DC and GM-DC were prepared by culturing mouse bone marrow cells with complete DMEM supplemented, respectively, with 15% of flt3 ligand-containing and 10% GM-CSF-containing conditioned medium for 7 to 8 days (10,21,35).…”

Section: Characterization Of Il-4-inducing Factor-mentioning

confidence: 99%

“…The activated DC and signals induced by cytokines together regulate Th1/Th2 development (9). In malaria, DC are the major early responders that produce pro-inflammatory cytokines, leading to NK and T cell activation and IFN-γ production (10)(11)(12). IFN-γ contributes to parasitemia control by priming phagocytes for clearance of parasites (13).…”

Section: Introductionmentioning

confidence: 99%

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A malaria protein factor induces IL-4 production by dendritic cells via PI3K–Akt–NF-κB signaling independent of MyD88/TRIF and promotes Th2 response

Wu¹,

Gowda²,

Kawasawa

et al. 2018

Journal of Biological Chemistry

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Dendritic cells (DC) and cytokines produced by DC play crucial roles in inducing and regulating pro-/anti-inflammatory and Th1/Th2 responses. DC are known to produce Th1-promoting cytokine, IL-12, in response to malaria and other pathogenic infections, but it is thought that DC do not produce Th2-promoting cytokine, IL-4. Here, we show that a protein factor of malaria parasites induces IL-4 responses by CD11c hi MHCII hi CD3ε -

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E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP‐1 Proteasomal Degradation

Liu,

Wang,

Liu

et al. 2024

Advanced Science

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As a highly organized system, endo‐lysosomes play a crucial role in maintaining immune homeostasis. However, the mechanisms involved in regulating endo‐lysosome progression and subsequent inflammatory responses are not fully understood. By screening 103 E3 ubiquitin ligases in regulating endo‐lysosomal acidification, it is discovered that lysosomal RNF13 inhibits lysosome maturation and promotes inflammatory responses mediated by endosomal Toll‐like receptors (TLRs) in macrophages. Mechanistically, RNF13 mediates K48‐linked polyubiquitination of LAMP‐1 at residue K128 for proteasomal degradation. Upon TLRs activation, LAMP‐1 promotes lysosomes maturation, which accelerates lysosomal degradation of TLRs and reduces TLR signaling in macrophages. Furthermore, peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA) show increased RNF13 levels and decreased LAMP‐1 expression. Accordingly, the immunosuppressive agent hydroxychloroquine (HCQ) can increase the polyubiquitination of RNF13. Taken together, the study establishes a linkage between proteasomal and lysosomal degradation mechanisms for the induction of appropriate innate immune response, and offers a promising approach for the treatment of inflammatory diseases by targeting intracellular TLRs.

show abstract

Phagosomal Acidification Prevents Macrophage Inflammatory Cytokine Production to Malaria, and Dendritic Cells Are the Major Source at the Early Stages of Infection

Cited by 28 publications

References 53 publications

Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism

Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism

A malaria protein factor induces IL-4 production by dendritic cells via PI3K–Akt–NF-κB signaling independent of MyD88/TRIF and promotes Th2 response

E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP‐1 Proteasomal Degradation

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