Azithromycin modulates immune response of human monocyte-derived dendritic cells and CD4 + T cells

Lin, Syh‐Jae; Kuo, Ming‐Ling; Hsiao, Hsiu-Shan; Lee, Pei-Tzu

doi:10.1016/j.intimp.2016.09.012

Cited by 51 publications

(52 citation statements)

References 35 publications

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“…Azithromycin has immunomodulatory properties independent of its antimicrobial function that are exploited in the treatment of chronic inflammatory diseases, such as asthma ( 17 , 18 ), COPD ( 19 ), and non-cystic fibrosis bronchiectasis ( 20 ). In general, AZM promotes an anti-inflammatory environment by shifting macrophages from the inflammatory M1 toward the anti-inflammatory M2 phenotype ( 21 , 22 ), by reducing the activation of mo-DCs as well as their stimulatory effect on CD4 T cells in vitro ( 23 ), and by directly suppressing CD4 T cell activation through inhibition of mTOR activity ( 24 ). We found that treatment of mice with AZM 7 or 14 dpc with B. pertussis significantly reduced the number of neutrophils, macrophages, and mo-DCs in the lungs.…”

Section: Discussionmentioning

confidence: 99%

“…The reduced activation status of antigen-presenting cells after AZM treatment at 7 dpc might also impair T cell activation. It has been reported that human mo-DCs induced in vitro in the presence of AZM have reduced activation and capacity to induce T cell proliferation ( 23 ). However, a loss of PAMPs due to antimicrobial activity of AZM is a more likely explanation for the reduced T cells activation that we observed in our in vivo experiments with B. pertussis infection.…”

Section: Discussionmentioning

confidence: 99%

“…Independent of their antimicrobial properties, macrolide antibiotics are known to have immunomodulatory properties, and are used in the treatment of several chronic inflammatory diseases, such as asthma ( 17 , 18 ), chronic obstructive pulmonary disease (COPD) ( 19 ), and non-cystic fibrosis bronchiectasis ( 20 ). AZM has been shown to shift the phenotype of macrophages from the inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype ( 21 , 22 ), to reduce the expression of activation markers CD80 and CD86 on monocyte-derived DCs (mo-DCs) ( 23 ), and to suppress CD4 T cell activation ( 24 ). While these effects can have a positive effect in chronic inflammatory conditions, they might prove detrimental during the induction of protective immunity against infection.…”

Section: Introductionmentioning

confidence: 99%

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Azithromycin Clears Bordetella pertussis Infection in Mice but Also Modulates Innate and Adaptive Immune Responses and T Cell Memory

et al. 2018

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Treatment with the macrolide antibiotic azithromycin (AZM) is an important intervention for controlling infection of children with Bordetella pertussis and as a prophylaxis for preventing transmission to family members. However, antibiotics are known to have immunomodulatory effects independent of their antimicrobial activity. Here, we used a mouse model to examine the effects of AZM treatment on clearance of B. pertussis and induction of innate and adaptive immunity. We found that treatment of mice with AZM either 7 or 14 days post challenge effectively cleared the bacteria from the lungs. The numbers of innate immune cells in the lungs were significantly reduced in antibiotic-treated mice. Furthermore, AZM reduced the activation status of macrophages and dendritic cells, but only in mice treated on day 7. Early treatment with antibiotics also reduced the frequency of tissue-resident T cells and IL-17-producing cells in the lungs. To assess the immunomodulatory effects of AZM independent of its antimicrobial activity, mice were antibiotic treated during immunization with a whole cell pertussis (wP) vaccine. Protection against B. pertussis induced by immunization with wP was slightly reduced in AZM-treated mice. Antibiotic-treated wP-immunized mice had reduced numbers of lung-resident memory CD4 T cells and IL-17-production and reduced CD49d expression on splenic CD4 T cells after challenge, suggestive of impaired CD4 T cell memory. Taken together these results suggest that AZM can modulate the induction of memory CD4 T cells during B. pertussis infection, but this may in part be due to the clearance of B. pertussis and resulting loss of components that stimulate innate and adaptive immune response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Azithromycin Clears Bordetella pertussis Infection in Mice but Also Modulates Innate and Adaptive Immune Responses and T Cell Memory

et al. 2018

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“…Tissue damage is known to stimulate the production of INF‐γ by dendritic cells, which increases cytokines involved in elevating body temperature (eg, TNF‐α and IL‐6) by macrophage activation. Syh‐Jae Lin et al reported that AZM reduces the expression of CD80, CD86, and HLA‐DR in dendritic cells stimulated by lipopolysaccharides (LPSs) to suppress the production of IL‐6, IL‐10, IL‐12, and TNF‐α in these cells . This suggests that AZM may have systemic effects and suppresses the cytokines involved in elevating body temperature.…”

Section: Discussionmentioning

confidence: 99%

Biological responses following one‐stage full‐mouth scaling and root planing with and without azithromycin: Multicenter randomized trial

Yashima

Morozumi

Yoshie

et al. 2019

J of Periodontal Research

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Background and Objective Full‐mouth scaling and root planing (FM‐SRP) increases the systemic levels of inflammatory mediators via early inflammation but may be inhibited using an antimicrobial agent. This prospective intervention study evaluates the biological response and clinical effects of FM‐SRP with and without systemically administered azithromycin (AZM). Materials and Methods A multicenter parallel randomized controlled and open‐label trial. A central randomization center used computer‐generated tables to allocate treatments. Sixty‐three patients with moderate to severe generalized periodontitis (New American Academy of Periodontology Classification: Stage3 or 4, Grade B) were randomly assigned to receive FM‐SRP with AZM (test group, n = 32) or FM‐SRP without AZM (control group, n = 31). Clinical parameters and body temperature were measured, and subgingival plaque, peripheral blood, and gingival crevicular fluid were collected before and after treatment. Periodontopathic bacteria and IgG titers were measured by gingival crevicular fluid and peripheral blood. High‐sensitivity assays were used to analyze systemic and local inflammatory markers, such as endotoxin, high‐sensitive CRP (hs‐CRP), and six inflammatory cytokines. Follow‐up 6 weeks. Results The total number of bacteria and the number of Porphyromonas gingivalis and Prevotella intermedia were significantly lower in the test group after FM‐SRP. IgG titers for P gingivalis significantly decreased after FM‐SRP with AZM, and the body temperature increased significantly after FM‐SRP without AZM. In the control group, serum hs‐CRP, IFN‐γ, IL‐12p70, and IL‐6 were significantly increased one day after treatment, but subsequently decreased below the original numerical value. In the test group, only hs‐CRP showed a significant increase. Conclusions FM‐SRP resulted in similar improvements in clinical parameters with and without the use of AZM. Inflammatory mediators showed no difference between the two groups after FM‐SRP treatment. The use of AZM was effective in preventing the elevation of body temperature after FM‐SRP.

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“…Besides this, azithromycin is known to have an anti-inflammatory action [3] and it is possible that the beneficial effect seen in the azithromycin group may be due to this.…”

mentioning

confidence: 99%

In reference to ‘Therapeutic efficacy of azithromycin and acetylcysteine in chronic otitis media with effusion’

Bakshi

2017

Eur Arch Otorhinolaryngol

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Azithromycin modulates immune response of human monocyte-derived dendritic cells and CD4 + T cells

Cited by 51 publications

References 35 publications

Azithromycin Clears Bordetella pertussis Infection in Mice but Also Modulates Innate and Adaptive Immune Responses and T Cell Memory

Azithromycin Clears Bordetella pertussis Infection in Mice but Also Modulates Innate and Adaptive Immune Responses and T Cell Memory

Biological responses following one‐stage full‐mouth scaling and root planing with and without azithromycin: Multicenter randomized trial

In reference to ‘Therapeutic efficacy of azithromycin and acetylcysteine in chronic otitis media with effusion’

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