Genome-Wide Transcriptional Analysis Reveals Novel AhR Targets That Regulate Dendritic Cell Function during Influenza A Virus Infection

Abstract

Activation of the ligand inducible aryl hydrocarbon receptor (AhR) during primary influenza A virus infection diminishes host responses by negatively regulating the ability of dendritic cells (DC) to prime naive CD8 + T cells, which reduces the generation of CTL. However, AhR-regulated genes and signaling pathways in DCs are not fully known. In this study, we used unbiased gene expression profiling to identify differentially expressed genes and signaling pathways in DCs that are modulated by AhR activation in vivo. Using the prototype AhR agonist TCDD, we identified the lectin receptor Cd209a (DC-SIGN) and chemokine Ccl17 as novel AhR target genes. We further show the percentage of DCs expressing CD209a on their surface was significantly decreased by AhR activation during infection. Whereas influenza A virus infection increased CCL17 protein levels in the lung and lung-draining lymph nodes, this was significantly reduced following AhR activation. Targeted excision of AhR in the hematopoietic compartment confirmed AhR is required for downregulation of CCL17 and CD209a. Loss of AhR's functional DNA-binding domain demonstrates that AhR activation alone is necessary but not sufficient to drive downregulation. AhR activation induced similar changes in gene expression in human monocyte-derived DCs. Analysis of the murine and human upstream regulatory regions of Cd209a and Ccl17 revealed a suite of potential transcription factor partners for AhR, which may coregulate these genes in vivo. This study highlights the breadth of AhR-regulated pathways within DCs, and that AhR likely interacts with other transcription factors to modulate DC functions during infection.

Redox control in the pathophysiology of influenza virus infection

“…These studies suggest the importance of the AhR activation during development in DCs. Franhini et al reported the genome-wide transcription map of AhR targets genes induced by influenza virus H3N2 in dendritic cells and found that the lectin receptor Cd209a (DC-SIGN) and chemokine the Ccl17 are novel AhR target genes [167].…”

Effects of rapid rehabilitation nursing on surgical‐site wound infection and postoperative complications of patients undergoing thoracoscopic lung cancer surgery: A meta‐analysis

“…Wound infection, a postoperative complication due to bacterial invasion, can lead to additional complications like incisional hernia and sepsis, prolonging recovery and imposing significant physical, psychological, and financial burdens on patients 43 . This study reveals that rapid rehabilitation nursing significantly reduces the incidence of wound infections in thoracoscopic lung cancer surgery patients by providing tailored nursing care that enhances wound care postoperatively and fosters wound healing 44 …”

Effects of refined nursing interventions in the operating room on surgical‐site wound infection in patients with lung cancer: A meta‐analysis

“…However, there are still problems with this procedure, such as surgical‐site wound infection and postoperative lung infection. Surgical‐site wound infection occurs due to bacterial invasion of the incision in the perioperative period, which increases the incidence of complications such as incisional hernia and sepsis, prolongs the hospital stay and imposes a major psychological and economic burden on the patient 8 . Therefore, clinical interventions to reduce the incidence of surgical‐site wound infection should be implemented as soon as possible to improve the prognosis and well‐being of patients.…”

“…Surgical-site wound infection occurs due to bacterial invasion of the incision in the perioperative period, which increases the incidence of complications such as incisional hernia and sepsis, prolongs the hospital stay and imposes a major psychological and economic burden on the patient. 8 Therefore, clinical interventions to reduce the incidence of surgical-site wound infection should be implemented as soon as possible to improve the prognosis and well-being of patients. Antimicrobials are commonly used clinically to prevent and treat perioperative infections; however, the use of antimicrobials tends to increase the metabolic burden on liver function and has a limited preventive effect.…”