scholarly journals Bordetella pertussisAdenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Shakir Hasan ◽  
Nikhil Nitin Kulkarni ◽  
Arni Asbjarnarson ◽  
Irena Linhartova ◽  
Radim Osicka ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Immune Defense ◽  
Innate Immune ◽  
Camp Signaling ◽  
Apical Surface ◽  
Bronchial Epithelial ◽  
Content Type ◽  
Functional Integrity ◽  
Cell Layers

ABSTRACTThe airway epithelium restricts the penetration of inhaled pathogens into the underlying tissue and plays a crucial role in the innate immune defense against respiratory infections. The whooping cough agent,Bordetella pertussis, adheres to ciliated cells of the human airway epithelium and subverts its defense functions through the action of secreted toxins and other virulence factors. We examined the impact ofB. pertussisinfection and of adenylate cyclase toxin-hemolysin (CyaA) action on the functional integrity of human bronchial epithelial cells cultured at the air-liquid interface (ALI).B. pertussisadhesion to the apical surface of polarized pseudostratified VA10 cell layers provoked a disruption of tight junctions and caused a drop in transepithelial electrical resistance (TEER). The reduction of TEER depended on the capacity of the secreted CyaA toxin to elicit cAMP signaling in epithelial cells through its adenylyl cyclase enzyme activity. Both purified CyaA and cAMP-signaling drugs triggered a decrease in the TEER of VA10 cell layers. Toxin-produced cAMP signaling caused actin cytoskeleton rearrangement and induced mucin 5AC production and interleukin-6 (IL-6) secretion, while it inhibited the IL-17A-induced secretion of the IL-8 chemokine and of the antimicrobial peptide beta-defensin 2. These results indicate that CyaA toxin activity compromises the barrier and innate immune functions ofBordetella-infected airway epithelia.

scholarly journals Pseudomonas aeruginosa Suppresses Interferon Response to Rhinovirus Infection in Cystic Fibrosis but Not in Normal Bronchial Epithelial Cells

2011 ◽  
Vol 79 (10) ◽  
pp. 4131-4145 ◽  
Author(s):  
Sangbrita S. Chattoraj ◽  
Shyamala Ganesan ◽  
Andrea Faris ◽  
Adam Comstock ◽  
Wai-Ming Lee ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Bronchial Epithelial Cells ◽  
Innate Immune ◽  
Interferon Response ◽  
Innate Immune Responses ◽  
Normal Cells ◽  
Bronchial Epithelial ◽  
Content Type ◽  
Infected Cells

ABSTRACTDespite increased morbidity associated with secondary respiratory viral infections in cystic fibrosis (CF) patients with chronicPseudomonas aeruginosainfection, the underlying mechanisms are not well understood. Here, we investigated the effect ofP. aeruginosainfection on the innate immune responses of bronchial epithelial cells to rhinovirus (RV) infection. CF cells sequentially infected with mucoidP. aeruginosa(MPA) and RV showed lower levels of interferons (IFNs) and higher viral loads than those of RV-infected cells. Unlike results for CF cells, normal bronchial epithelial cells coinfected with MPA/RV showed higher IFN expression than RV-infected cells. In both CF and normal cells, the RV-stimulated IFN response requires phosphorylation of Akt and interferon response factor 3 (IRF3). Preinfection with MPA inhibited RV-stimulated Akt phosphorylation and decreased IRF3 phosphorylation in CF cells but not in normal cells. Compared to normal, unstimulated CF cells or normal cells treated with CFTR inhibitor showed increased reactive oxygen species (ROS) production. Treatment of CF cells with antioxidants prior to MPA infection partially reversed the suppressive effect of MPA on the RV-stimulated IFN response. Together, these results suggest that MPA preinfection inhibits viral clearance by suppressing the antiviral response particularly in CF cells but not in normal cells. Further, increased oxidative stress in CF cells appears to modulate the innate immune responses to coinfection.

scholarly journals The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

2013 ◽  
Vol 82 (3) ◽  
pp. 1112-1122 ◽  
Author(s):  
Pradeep Bist ◽  
Neha Dikshit ◽  
Tse Hsien Koh ◽  
Alessandra Mortellaro ◽  
Thuan Tong Tan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Acinetobacter Baumannii ◽  
Airway Epithelial Cells ◽  
Immune Defense ◽  
Innate Immune ◽  
Lung Epithelial Cells ◽  
Airway Epithelial ◽  
Content Type ◽  
Mitogen Activated Protein

ABSTRACTAcinetobacter baumanniiis a major extensively drug-resistant lethal human nosocomial bacterium. However, the host innate immune mechanisms controllingA. baumanniiare not well understood. Although viewed as an extracellular pathogen,A. baumanniican also invade and survive intracellularly. However, whether host innate immune pathways sensing intracellular bacteria contribute to immunity againstA. baumanniiis not known. Here, we provide evidence for the first time that intracellular antibacterial innate immune receptors Nod1 and Nod2, and their adaptor Rip2, play critical roles in the sensing and clearance ofA. baumanniiby human airway epithelial cellsin vitro.A. baumanniiinfection upregulated Rip2 expression. Silencing of Nod1, Nod2, and Rip2 expression profoundly increased intracellular invasion and prolonged the multiplication and survival ofA. baumanniiin lung epithelial cells. Notably, the Nod1/2-Rip2 axis did not contribute to the control ofA. baumanniiinfection of human macrophages, indicating that they play cell type-specific roles. The Nod1/2-Rip2 axis was needed forA. baumanniiinfection-induced activation of NF-κB but not mitogen-activated protein kinases. Moreover, the Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine responses toA. baumanniiinfection. Mechanistic studies showed that the Nod1/2 pathway contributed to the innate control ofA. baumanniiinfection through the production of β-defensin 2 by airway epithelial cells. This study revealed new insights into the immune control ofA. baumanniiand may contribute to the development of effective immune therapeutics and vaccines againstA. baumannii.

Flagellin induces innate immune genes in bronchial epithelial cells in vivo: Role of TET2

2021 ◽  
Author(s):  
Wanhai Qin ◽  
Xanthe Brands ◽  
Cornelis Veer ◽  
Alex F. Vos ◽  
Brendon P. Scicluna ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Innate Immune ◽  
Bronchial Epithelial ◽  
Immune Genes ◽  
Innate Immune Genes

scholarly journals Combined Stimulation of Toll-Like Receptor 5 and NOD1 Strongly Potentiates Activity of NF-κB, Resulting in Enhanced Innate Immune Reactions and Resistance to Salmonella enterica Serovar Typhimurium Infection

2013 ◽  
Vol 81 (10) ◽  
pp. 3855-3864 ◽  
Author(s):  
Amir I. Tukhvatulin ◽  
Ilya I. Gitlin ◽  
Dmitry V. Shcheblyakov ◽  
Natalia M. Artemicheva ◽  
Lyudmila G. Burdelya ◽  
...  
Keyword(s):  
Critical Role ◽  
Immune Defense ◽  
Innate Immune ◽  
Microbial Infection ◽  
Immune Reactions ◽  
Content Type ◽  
Essential Components ◽  
Stimulation Of

ABSTRACTPathogen recognition receptors (PRRs) are essential components of host innate immune systems that detect specific conserved pathogen-associated molecular patterns (PAMPs) presented by microorganisms. Members of two families of PRRs, transmembrane Toll-like receptors (TLRs 1, 2, 4, 5, and 6) and cytosolic NOD receptors (NOD1 and NOD2), are stimulated upon recognition of various bacterial PAMPs. Such stimulation leads to induction of a number of immune defense reactions, mainly triggered via activation of the transcription factor NF-κB. While coordination of responses initiated via different PRRs sensing multiple PAMPS present during an infection makes clear biological sense for the host, such interactions have not been fully characterized. Here, we demonstrate that combined stimulation of NOD1 and TLR5 (as well as other NOD and TLR family members) strongly potentiates activity of NF-κB and induces enhanced levels of innate immune reactions (e.g., cytokine production) bothin vitroandin vivo. Moreover, we show that an increased level of NF-κB activity plays a critical role in formation of downstream responses. In live mice, synergy between these receptors resulting in potentiation of NF-κB activity was organ specific, being most prominent in the gastrointestinal tract. Coordinated activity of NOD1 and TLR5 significantly increased protection of mice against enteroinvasiveSalmonellainfection. Obtained results suggest that cooperation of NOD and TLR receptors is important for effective responses to microbial infectionin vivo.

scholarly journals Cooperative Immune Suppression by Escherichia coli and Shigella Effector Proteins

2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Maarten F. de Jong ◽  
Neal M. Alto
Keyword(s):  
Escherichia Coli ◽  
Defense Mechanisms ◽  
Immune Defense ◽  
Effector Proteins ◽  
Innate Immune ◽  
Host Cells ◽  
Secretion Systems ◽  
Content Type ◽  
E Coli ◽  
Type Iii Secretion Systems

ABSTRACT The enteric attaching and effacing (A/E) pathogens enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) and the invasive pathogens enteroinvasive E. coli (EIEC) and Shigella encode type III secretion systems (T3SS) used to inject effector proteins into human host cells during infection. Among these are a group of effectors required for NF-κB-mediated host immune evasion. Recent studies have identified several effector proteins from A/E pathogens and EIEC/ Shigella that are involved in suppression of NF-κB and have uncovered their cellular and molecular functions. A novel mechanism among these effectors from both groups of pathogens is to coordinate effector function during infection. This cooperativity among effector proteins explains how bacterial pathogens are able to effectively suppress innate immune defense mechanisms in response to diverse classes of immune receptor signaling complexes (RSCs) stimulated during infection.

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