Induction of Proinflammatory Cytokines from Human Respiratory Epithelial Cells after Stimulation by Nontypeable<i>Haemophilus influenzae</i>

Clemans, Daniel L.; Bauer, Richard J.; Hanson, Julie A.; Hobbs, Monte V.; Geme, Joseph W. St.; Marrs, Carl F.; Gilsdorf, Janet R.

doi:10.1128/iai.68.8.4430-4440.2000

Cited by 52 publications

(46 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Diverse microbial pathogens stimulate airway epithelial cells, leading to activation of the transcriptional activator NF-B and production of proinflammatory cytokines, such as IL-6 and IL-8 (5,15,20,28,30). In this study, we observed that CS inhibited IL-8 production brought about by NT H. influenzae and S. aureus in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 54%

Cigarette Smoke Inhibits Airway Epithelial Cell Innate Immune Responses to Bacteria

Rampersaud¹,

Aguilar²,

Randis³

et al. 2010

Infect Immun

View full text Add to dashboard Cite

The human upper respiratory tract, including the nasopharynx, is colonized by a diverse array of microorganisms. While the host generally exists in harmony with the commensal microflora, under certain conditions, these organisms may cause local or systemic disease. Respiratory epithelial cells act as local sentinels of the innate immune system, responding to conserved microbial patterns through activation of signal transduction pathways and cytokine production. In addition to colonizing microbes, these cells may also be influenced by environmental agents, including cigarette smoke (CS). Because of the strong relationship among secondhand smoke exposure, bacterial infection, and sinusitis, we hypothesized that components in CS might alter epithelial cell innate immune responses to pathogenic bacteria. We examined the effect of CS condensate (CSC) or extract (CSE) on signal transduction and cytokine production in primary and immortalized epithelial cells of human or murine origin in response to nontypeable Haemophilus influenzae and Staphylococcus aureus. We observed that epithelial production of interleukin-8 (IL-8) and IL-6 in response to bacterial stimulation was significantly inhibited in the presence of CS (P < 0.001 for inhibition by either CSC or CSE). In contrast, epithelial production of beta interferon (IFN-␤) was not inhibited. CSC decreased NF-B activation (P < 0.05) and altered the kinetics of mitogen-activated protein kinase phosphorylation in cells exposed to bacteria. Treatment of CSC with antioxidants abrogated CSC-mediated reduction of epithelial IL-8 responses to bacteria (P > 0.05 compared to cells without CSC treatment). These results identify a novel oxidant-mediated immunosuppressive role for CS in epithelial cells.

show abstract

Section: Discussionsupporting

confidence: 54%

Cigarette Smoke Inhibits Airway Epithelial Cell Innate Immune Responses to Bacteria

Rampersaud¹,

Aguilar²,

Randis³

et al. 2010

Infect Immun

View full text Add to dashboard Cite

show abstract

“…In our model, we did detect proinflammatory cytokines at early time points postinfection, suggesting that nonmacrophage lung cells are capable of compensating for the absence of AMs. We suggest that epithelial cells are responsible for the observed early cytokine production and for triggering neutrophil recruitment, as epithelial cells can produce IL-8 in response to influenza virus and IL-6, IL-1␣, IL-1␤, and TNF-␣ in response to Haemophilus influenzae (51,52). Ongoing studies are focused on elucidating the effects of S. marcescens on epithelial cell cytokine production.…”

Section: Discussionmentioning

confidence: 99%

Requirement for Serratia marcescens Cytolysin in a Murine Model of Hemorrhagic Pneumonia

Mares¹,

Medina²,

Cantwell³

et al. 2015

Infect Immun

View full text Add to dashboard Cite

Serratia marcescens, a member of the carbapenem-resistant Enterobacteriaceae, is an important emerging pathogen that causes a wide variety of nosocomial infections, spreads rapidly within hospitals, and has a systemic mortality rate of <41%. Despite multiple clinical descriptions of S. marcescens nosocomial pneumonia, little is known regarding the mechanisms of bacterial pathogenesis and the host immune response. To address this gap, we developed an oropharyngeal aspiration model of lethal and sublethal S. marcescens pneumonia in BALB/c mice and extensively characterized the latter. Lethal challenge (>4.0 ؋ 10 6 CFU) was characterized by fulminate hemorrhagic pneumonia with rapid loss of lung function and death. Mice challenged with a sublethal dose (<2.0 ؋ 10 6 CFU) rapidly lost weight, had diminished lung compliance, experienced lung hemorrhage, and responded to the infection with extensive neutrophil infiltration and histopathological changes in tissue architecture. Neutrophil extracellular trap formation and the expression of inflammatory cytokines occurred early after infection. Mice depleted of neutrophils were exquisitely susceptible to an otherwise nonlethal inoculum, thereby demonstrating the requirement for neutrophils in host protection. Mutation of the genes encoding the cytolysin ShlA and its transporter ShlB resulted in attenuated S. marcescens strains that failed to cause profound weight loss, extended illness, hemorrhage, and prolonged lung pathology in mice. This study describes a model of S. marcescens pneumonia that mimics known clinical features of human illness, identifies neutrophils and the toxin ShlA as a key factors important for defense and infection, respectively, and provides a solid foundation for future studies of novel therapeutics for this important opportunistic pathogen. Serratia marcescens is a facultative anaerobic, rod-shaped, Gram-negative bacterium that is ubiquitous in water, in soil, and on plant surfaces. S. marcescens is also an antibiotic-resistant opportunistic pathogen and is among the top 10 causative agents of bloodstream bacterial infections in North America, with a mortality rate of 41% (1-3). In newborns and immunocompromised and intensive care patients, S. marcescens can cause severe infections such as pneumonia (4), bloodstream infections (5), and urinary tract infections, surgical site infections, and ocular infections (6). S. marcescens infections are most often associated with the hospital environment (5), but community-acquired infections are now increasingly diagnosed (7).S. marcescens has acquired notoriety in the last 20 years because of its resistance to multiple antibiotics (7,8). An 8-year surveillance study in Taiwan identified multiple S. marcescens strains that were resistant to the antibiotics ciprofloxacin and levofloxacin (9). Multiple studies have revealed an alarming increase in S. marcescens resistance to carbapenem and other ␤-lactam antibiotics (8, 10, 11). As such, S. marcescens is considered a member of the carbapenem-resistant Enterobac...

show abstract

“…A further possibility is that release of Hap facilitates the degradation of target host proteins such as tissue components or immune system effectors. Interestingly, the first experiments to find a Hapimmune system interaction have shown that Hap does not induce proinflammatory cytokines from human respiratory epithelial cells but that immunization with the purified protein does protect mice against nasopharyngeal colonization with wild-type organisms (68,86).…”

Section: H Influenzae Adhesion and Penetration Protein (Hap)mentioning

confidence: 99%

“…68,2004 TYPE V SECRETION 695 signal sequence which targets proteins for secretion to the Sec inner membrane secretion pathway (for in-depth reviews, see references 115; 245; and 509). The Sec machinery is composed of an ATPase, SecA, several integral inner membrane proteins (SecD, SecE, SecF, SecG, and SecY, and a signal peptidase (116,338).…”

Section: Two-step Type II Protein Secretionmentioning

confidence: 99%

Type V Protein Secretion Pathway: the Autotransporter Story

Henderson

Navarro-Garcı́a

Desvaux

et al. 2004

Microbiol Mol Biol Rev

713

795

View full text Add to dashboard Cite

Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function

show abstract

Induction of Proinflammatory Cytokines from Human Respiratory Epithelial Cells after Stimulation by NontypeableHaemophilus influenzae

Cited by 52 publications

References 70 publications

Cigarette Smoke Inhibits Airway Epithelial Cell Innate Immune Responses to Bacteria

Cigarette Smoke Inhibits Airway Epithelial Cell Innate Immune Responses to Bacteria

Requirement for Serratia marcescens Cytolysin in a Murine Model of Hemorrhagic Pneumonia

Type V Protein Secretion Pathway: the Autotransporter Story

Contact Info

Product

Resources

About