RANK Ligand Helps Immunity to Leishmania major by Skewing M2-Like Into M1 Macrophages

Rigoni, Thaís S; Vellozo, Natália S.; Cabral-Piccin, Mariela Pires; Fabiano-Coelho, Laryssa; Lopes, Ulisses Gazos; Filardy, Alessandra A.; DosReis, George A.; Lopes, Marcela F.

doi:10.3389/fimmu.2020.00886

Cited by 9 publications

(12 citation statements)

References 61 publications

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“…Fibroblast apoptosis is also induced by upregulating collagenolytic enzymes, prostaglandin E2 (PGE2) and chemokines [ 17 ]. Meanwhile, anti-inflammatory factors can downregulate pro-inflammatory factors and RANKL expression in activated T cells, thereby inhibiting osteoclastogenesis [ 18 ]. Type II diabetes mellitus (T2DM) is a type of metabolic disease caused by deficiency of insulin, where the pathogenesis thereof principally includes insufficient insulin production, insulin malfunction, and lack of insulin receptors on the cell surface, resulting in decreased glucose tolerance and increased blood sugar.…”

Section: Introductionmentioning

confidence: 99%

Effects of statins on cytokines levels in gingival crevicular fluid and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus

Zhang

Chen

et al. 2021

PLoS ONE

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Objective To analyze the effect of statins on cytokines levels in gingival crevicular fluid (GCF) and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). Methods Systemically healthy controls (C group, n = 62), T2DM patients not taking statins (D group, n = 57) and T2DM patients taking statins (S group, n = 24) were recruited. In each group, subjects (40–85 years) were subclassified into the h (periodontal health)group, the g (gingivitis)group or the p (periodontitis) group according to different periodontal conditions. 17 cytokines in gingival crevicular fluid (GCF) and saliva samples of each subject were measured utilizing the Luminex technology kit. Further, HbA1c (glycated hemoglobin), FPG (fasting plasma glucose), PD (probing depth), CAL (clinical attachment level), BOP (bleeding on probing), GI (gingival index) and PI (periodontal index) were recorded. Data distribution was tested through the Shapiro-Wilk test, upon which the Kruskal-Wallis test was applied followed by Mann-Whitney U test and Bonferroni’s correction. Results Levels of IFN-γ, IL-5, IL-10 and IL-13 in the saliva of the Dh group were significantly lower than those in the Ch group, while factor IL-4 was higher (p<0.05). Levels of MIP-3α, IL-7 and IL-2 in GCF of the Dh group were considerably higher than those in the Ch group (p<0.05), while that of IL-23 was considerably lower. Compared with the Cg group, levels of IFN-γ, IL-4, IL-5, IL-6, IL-10 and IL-13 were significantly lower in the saliva of the Dg group (p<0.05). Lower levels of IFN-γ, IL-5 and IL-10 were detected in the Sg group than those in the Cg group (p<0.05). At the same time, levels of IL-1β, IL-6, IL-7, IL-13, IL-17, IL-21 and MIP-3α in the gingival crevicular fluid of the Sg group were lower in comparison with the Dg group. In addition, lower levels of IL-4 and higher levels of IL-7 in GCF were identified in the Dg group than those in the Cg group, while in the Sg group, lower levels of IL-4, MIP-1αand MIP-3αwere observed than those in the Cg group (p<0.05). Lower levels of IFN-γ, IL-6, IL-10, IL-13 and I-TAC were found in the Sp group compared with those in the Cp group. The IFN-γ, IL-6 and IL-10 levels were lower in the Dp group than those in the Cp group (p<0.05). Meanwhile, in the Sp group, lower levels of pro-inflammatory factors IFN-γ, IL-1β, IL-2, IL-6, IL-7, IL-21 and TNF-α, in addition to higher levels of anti-inflammatory factors IL-4 and IL-5 in gingival crevicular fluid, were identified than those in the Dp group. Higher levels of IFN-γ,IL-1β,IL-2,IL-7,IL-21 and TNF-α and a lower level of IL-5 in the Dp group were identified than those in the Cp group (p<0.05). Moreover, statins were able to substantially reduce PD in T2DM patients with periodontitis, indicating an obvious influence on the levels of cytokines secreted by Th1 cells, Th2 cells and Th17 cells, as revealed by PCA (principal component analysis). Conclusion Statins are associated with reduced PD and cytokines levels in the GCF and saliva of T2DM patients with periodontitis.

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Section: Introductionmentioning

confidence: 99%

Effects of statins on cytokines levels in gingival crevicular fluid and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus

Zhang

Chen

et al. 2021

PLoS ONE

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“…In addition, inflammatory monocytes from B6 mice expressed F4/80 int and a M2-like phenotype, characterized by heterogeneous expression of M2 markers such as MGL (CD301), mannose receptor (CD206), IL-4Ra and IL-10 (51). Strikingly, treatment with either RANKL or IFN-g induced monocytes to express F4/80 hi and M1 features, such as IL-12p35 and iNOS expression, IL-12 and TNF-a production, coupled with reduced M2 MGL marker (51). We also observed an intermediate M1-M2 subset, which expressed both MGL and iNOS after treatment with RANKL (51).…”

Section: Targeting Inflammatory Monocytes: Rankl Helps a M2-like To M1 Phenotype Shiftmentioning

confidence: 84%

“…We observed that monocytes secreted IL-12 in response to endogenous RANKL and IFN-g produced during the crosstalk between CD4 T-cells and infected monocytes. In turn, RANKL-stimulated monocytes increased Th1 responses (51). In the next section, we will discuss how RANKL and IFN-g affect the phenotype of inflammatory monocytes to promote immunity to L. major infection (51).…”

Section: Functional Monocyte Responses To Cd4 T-cell Cytokinesmentioning

confidence: 99%

“…In turn, RANKL-stimulated monocytes increased Th1 responses (51). In the next section, we will discuss how RANKL and IFN-g affect the phenotype of inflammatory monocytes to promote immunity to L. major infection (51).…”

Section: Functional Monocyte Responses To Cd4 T-cell Cytokinesmentioning

confidence: 99%

“…More importantly, RANKL and suboptimal IFN-g doses cooperated for the induction of fully-effector M1-macrophages, which showed higher iNOS/NO expression and killed L. major parasites in a NO and ROS-dependent fashion (51). Likewise, RANKL and IFN-g synergized to increase NO production by BALB/c inflammatory monocytes (51).…”

Section: Targeting Inflammatory Monocytes: Rankl Helps a M2-like To M1 Phenotype Shiftmentioning

confidence: 99%

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New Therapeutic Tools to Shape Monocyte Functional Phenotypes in Leishmaniasis

2021

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In the innate immunity to Leishmania infection tissue-resident macrophages and inflammatory monocytes accumulate host-cell, effector, and efferocytosis functions. In addition, neutrophils, as host, effector, and apoptotic cells, as well as tissue-resident and monocyte-derived dendritic cells (DCs) imprint innate and adaptive immunity to Leishmania parasites. Macrophages develop phenotypes ranging from antimicrobial M1 to parasite-permissive M2, depending on mouse strain, Leishmania species, and T-cell cytokines. The Th1 (IFN-γ) and Th2 (IL-4) cytokines, which induce classically-activated (M1) or alternatively-activated (M2) macrophages, underlie resistance versus susceptibility to leishmaniasis. While macrophage phenotypes have been well discussed, new developments addressed the monocyte functional phenotypes in Leishmania infection. Here, we will emphasize the role of inflammatory monocytes to access how potential host-directed therapies for leishmaniasis, such as all-trans-retinoic acid (ATRA) and the ligand of Receptor Activator of Nuclear Factor-Kappa B (RANKL) might modulate immunity to Leishmania infection, by directly targeting monocytes to develop M1 or M2 phenotypes.

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Role of Treg, Breg and other cytokine sets in host protection and immunopathology during human leishmaniasis: Are they potential valuable markers in clinical settings and vaccine evaluation?

et al. 2023

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RANK Ligand Helps Immunity to Leishmania major by Skewing M2-Like Into M1 Macrophages

Cited by 9 publications

References 61 publications

Effects of statins on cytokines levels in gingival crevicular fluid and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus

Effects of statins on cytokines levels in gingival crevicular fluid and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus

New Therapeutic Tools to Shape Monocyte Functional Phenotypes in Leishmaniasis

Role of Treg, Breg and other cytokine sets in host protection and immunopathology during human leishmaniasis: Are they potential valuable markers in clinical settings and vaccine evaluation?

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