scholarly journals Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16

2017 ◽  
Vol 8 ◽  
Author(s):  
Yang Xi ◽  
Niamh M. Troy ◽  
Denise Anderson ◽  
Olga M. Pena ◽  
Jason P. Lynch ◽  
...  
2020 ◽  
Author(s):  
Quentin Marquant ◽  
Daphné Laubreton ◽  
Carole Drajac ◽  
Elliot Mathieu ◽  
Edwige Bouguyon ◽  
...  

AbstractThe microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota can modulate reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific pathogen-free (SPF) and germ-free (GF) mice. Using SPF and GF mice intranasally exposed to lipopolysaccharide (LPS), a component of Gram-negative bacteria, we observed earlier and greater inflammation in the pulmonary compartment of GF mice than that of SPF mice. Toll-like receptor 4 (TLR4) was more abundantly expressed in the lungs of GF mice than those of SPF mice at steady state, which could predispose the innate immunity of GF mice to strongly react to environmental stimuli. Lung explants were stimulated with different TLR agonists or infected with the human airways pathogen, respiratory syncytial virus (RSV), resulting in greater inflammation under almost all conditions for the GF explants. Finally, alveolar macrophages (AM) from GF mice presented a higher innate immune response upon RSV infection than those of SPF mice. Overall, these data suggest that the presence of microbiota in SPF mice induced a process of innate immune tolerance in the lungs by a mechanism which remains to be elucidated. Our study represents a step forward to establishing the link between the microbiota and the immune reactivity of the lungs.Plain Language summaryMicrobiota represents an important partner of immunologic system at the interface between immune cells and epithelium. It is well known, notably in the gut, that the microbiota contributes in shaping efficient and safe defenses. However, little is known about the role of the microbiota in the education of pulmonary innate immune responses. In this study, we postulate that endogenous microbiota could dampen an excessive reactivity of pulmonary tissue to external stimuli. Thus, we sought to study the innate immune reaction switched on by viral or bacterial ligands in respiratory tract cells coming from mice with or without microbiota (germ-free condition, GF). Altogether, our results show a higher inflammatory reaction in GF condition. This study represents a step forward to better establish the link between the microbiota and the reactivity of the lung tissue. Not only these data demonstrate that the microbiota educates the pulmonary innate immune system, but also contributes the emerging concept of using respiratory commensal bacteria as potential next-generation probiotics to prevent susceptibility to respiratory diseases.


Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 323 ◽  
Author(s):  
Guoying Wang ◽  
Xianghui Li ◽  
Lei Zhang ◽  
Abualgasim Elgaili Abdalla ◽  
Tieshan Teng ◽  
...  

Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.


PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e78849 ◽  
Author(s):  
Thangam Sudha Velayutham ◽  
Deepthi Kolli ◽  
Teodora Ivanciuc ◽  
Roberto P. Garofalo ◽  
Antonella Casola

2010 ◽  
Vol 186 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Makoto Inoue ◽  
Yasuhiro Moriwaki ◽  
Tomohiro Arikawa ◽  
Yu-Hsun Chen ◽  
Young Joo Oh ◽  
...  

2021 ◽  
Vol 22 (17) ◽  
pp. 9228
Author(s):  
Guoshuai Cai ◽  
Mulong Du ◽  
Yohan Bossé ◽  
Helmut Albrecht ◽  
Fei Qin ◽  
...  

The current spreading coronavirus SARS-CoV-2 is highly infectious and pathogenic. In this study, we screened the gene expression of three host receptors (ACE2, DC-SIGN and L-SIGN) of SARS coronaviruses and dendritic cells (DCs) status in bulk and single cell transcriptomic datasets of upper airway, lung or blood of COVID-19 patients and healthy controls. In COVID-19 patients, DC-SIGN gene expression was interestingly decreased in lung DCs but increased in blood DCs. Within DCs, conventional DCs (cDCs) were depleted while plasmacytoid DCs (pDCs) were augmented in the lungs of mild COVID-19. In severe cases, we identified augmented types of immature DCs (CD22+ or ANXA1+ DCs) with MHCII downregulation. In this study, our observation indicates that DCs in severe cases stimulate innate immune responses but fail to specifically present SARS-CoV-2. It provides insights into the profound modulation of DC function in severe COVID-19.


2020 ◽  
Author(s):  
Ayantika Sen ◽  
Anil Kaul ◽  
Rashmi Kaul

AbstractThe bladder epithelial cells elicit robust innate immune responses against urinary tract infections (UTIs) for preventing the bacterial colonization. Physiological fluctuations in circulating estrogen levels in women increase the susceptibility to UTI pathogenesis, often resulting in adverse health outcomes. Dr adhesin bearing Escherichia coli (Dr E. coli) cause recurrent UTIs in menopausal women and acute pyelonephritis in pregnant women. Dr E. coli bind to epithelial cells via host innate immune receptor CD55, under hormonal influence. The role of estrogens or estrogen receptors (ERs) in regulating the innate immune responses in the bladder are poorly understood. In the current study, we investigated the role of ERα, ERβ and GPR30 in modulating the innate immune responses against Dr E. coli induced UTI using human bladder epithelial carcinoma 5637 cells (HBEC). Both ERα and ERβ agonist treatment in bladder cells induced a protection against Dr E. coli invasion via upregulation of TNFα and downregulation of CD55 and IL10, and these effects were reversed by action of ERα and ERβ antagoinsts. In contrast, the agonist-mediated activation of GPR30 led to an increased bacterial colonization due to suppression of innate immune factors in the bladder cells, and these effects were reversed by the antagonist-mediated suppression of GPR30. Further, siRNA-mediated ERα knockdown in the bladder cells reversed the protection against bacterial invasion observed in the ERα positive bladder cells, by modulating the gene expression of TNFα, CD55 and IL10, thus confirming the protective role of ERα. We demonstrate for the first time a protective role of nuclear ERs, ERα and ERβ but not of membrane ER, GPR30 against Dr E. coli invasion in HBEC 5637 cells. These findings have many clinical implications and suggest that ERs may serve as potential drug targets towards developing novel therapeutics for regulating local innate immunity and treating UTIs.HighlightsEstrogen receptor (ER) subtypes regulate the gene expression of innate immune molecules, CD55, TNFα and IL10 in human bladder epithelial cells impacting the bacterial colonization by Dr E. coli.Activation of nuclear ER subtypes, ERα and ERβ, upregulate the gene expression of proinflammatory cytokine, TNFα, but downregulate the gene expression of anti-inflammatory cytokine, IL10, and Dr E. coli colonization receptor, CD55, thus leading to efficient bacterial clearance in human bladder cells.In contrast, activation of the membrane ER subtype, GPR30, shows opposite effects to ERα and ERβ that were mediated on TNFα, IL10 and CD55 gene expression, thus leading to impaired bacterial clearance of Dr E. coli in human bladder cells.ER subtypes can serve as potential drug candidates for designing new therapies to boost or modulate the local immunity in the human bladder preventing the establishment of E. coli infections.


PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48655 ◽  
Author(s):  
Timothy R. Crother ◽  
Jun Ma ◽  
Madhulika Jupelli ◽  
Norika Chiba ◽  
Shuang Chen ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Huifang Zhu ◽  
Yan-Dong Tang ◽  
Guoqing Zhan ◽  
Chenhe Su ◽  
Chunfu Zheng

Poly (adenosine diphosphate-ribose) polymerases (PARPs) are a family of proteins responsible for transferring ADP-ribose groups to target proteins to initiate the ADP-ribosylation, a highly conserved and fundamental post-translational modification in all organisms. PARPs play important roles in various cellular functions, including regulating chromatin structure, transcription, replication, recombination, and DNA repair. Several studies have recently converged on the widespread involvement of PARPs and ADP-Ribosylation reaction in mammalian innate immunity. Here, we provide an overview of the emerging roles of PARPs family and ADP-ribosylation in regulating the host’s innate immune responses involved in cancers, pathogenic infections, and inflammations, which will help discover and design new molecular targets for cancers, pathogenic infections, and inflammations.


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