Moraxella catarrhalis lipooligosaccharide selectively upregulates ICAM-1 expression on human monocytes and stimulates adjacent naïve monocytes to produce TNF-α through cellular cross-talk

Xie, Hang; Gu, Xin-Xing

doi:10.1111/j.1462-5822.2008.01138.x

Cited by 26 publications

(23 citation statements)

References 52 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The M. catarrhalis lipooligosaccharides (LOS) (68) and the outer membrane protein UspA1 might be involved in stimulating the secretion of IL-8 in vitro (57), and MID/Hag might be involved in B-cell activation (47,67). Importantly, serum samples from COPD patients who had recently cleared M. catarrhalis infection are reactive to M. catarrhalis LOS (53) and MID/Hag (40), indicating that M. catarrhalis extracellular components may contribute to the production of inflammatory disease.…”

Section: Figmentioning

confidence: 99%

Bacterium-Generated Nitric Oxide Hijacks Host Tumor Necrosis Factor Alpha Signaling and Modulates the Host Cell Cycle In Vitro

Mocca

Wang

2012

J Bacteriol

View full text Add to dashboard Cite

In mammalian cells, nitric oxide (NO·) is an important signal molecule with concentration-dependent and often controversial functions of promoting cell survival and inducing cell death. An inducible nitric oxide synthase (iNOS) in various mammalian cells produces higher levels of NO· from L-arginine upon infections to eliminate pathogens. In this study, we reveal novel pathogenic roles of NO· generated by bacteria in bacterium-host cell cocultures using Moraxella catarrhalis, a respiratory tract disease-causing bacterium, as a biological producer of NO·. We recently demonstrated that M. catarrhalis cells that express the nitrite reductase (AniA protein) can produce NO· by reducing nitrite. Our study suggests that, in the presence of pathophysiological levels of nitrite, this opportunistic pathogen hijacks host cell signaling and modulates host gene expression through its ability to produce NO· from nitrite. Bacterium-generated NO· significantly increases the secretion of tumor necrosis factor alpha (TNF-␣) and modulates the expression of apoptotic proteins, therefore triggering host cell programmed death partially through TNF-␣ signaling. Furthermore, our study reveals that bacterium-generated NO· stalls host cell division and directly results in the death of dividing cells by reducing the levels of an essential regulator of cell division. This study provides unique insight into why NO· may exert more severe cytotoxic effects on fast growing cells, providing an important molecular basis for NO·-mediated pathogenesis in infections and possible therapeutic applications of NO·-releasing molecules in tumorigenesis. This study strongly suggests that bacterium-generated NO· can play important pathogenic roles during infections. In mammalian cells, nitric oxide (NO·) is a highly reactive and diffusible signaling molecule that plays key roles in modulating both physiological and pathological processes, such as immune response, cell survival, and cell death (reviewed in references 8 and 36). The diverse functions of NO· are often determined by its concentration or its source of production. Low levels of endogenous NO· are produced from L-arginine by constitutively expressed nitric oxide synthase in neuronal cells (nNOS, also known as NOS1) and endothelial cells (eNOS, also known as NOS3) to mediate normal physiological processes. Higher levels of NO· can be produced by an inducible nitric oxide synthase (iNOS, also known as NOS2) in different cell types, but mainly in macrophages, upon infection to kill pathogens (reviewed in reference 9). The higher levels of NO· produced by iNOS have been implicated in various human inflammatory diseases and neurodegenerative diseases (reviewed in references 9 and 12) and in chronic inflammation-related tumorigenesis (18, 33). Recent studies have also shown that chemical-generated higher levels of exogenous NO· can induce tumor cell apoptosis in vitro and in animal studies (37; reviewed in reference 1), raising interests in therapeutic exploration of NO·-releasing reagents as antitumor...

show abstract

Section: Figmentioning

confidence: 99%

Bacterium-Generated Nitric Oxide Hijacks Host Tumor Necrosis Factor Alpha Signaling and Modulates the Host Cell Cycle In Vitro

Mocca

Wang

2012

J Bacteriol

View full text Add to dashboard Cite

show abstract

“…It can potentially induce excessive inflammation via cellular cross-talk [11]. Unlike the outer membrane proteins such as MID, UspA, and CopB that show a great plasticity in their antigenicity [6], [23], the structures of LOS are highly conserved within each of the three serotypes of M. catarrhalis [12], [13].…”

Section: Discussionmentioning

confidence: 99%

“…catarrhalis . Being a major virulence factor of M. catarrhalis, LOS induces excessive inflammation via a Toll-like receptor 4 (TLR4) and CD14 dependent pathway [11]. The structures of LOS are conserved among 95% of known M. catarrhalis strains and clinical isolates [12], [13].…”

Section: Introductionmentioning

confidence: 99%

Intranasal Immunization of the Combined Lipooligosaccharide Conjugates Protects Mice from the Challenges with Three Serotypes of Moraxella catarrhalis

et al. 2011

Self Cite

View full text Add to dashboard Cite

BackgroundThere are no licensed vaccines available against Moraxella catarrhalis, a significant human respiratory pathogen. Lipooligosaccharide (LOS) based conjugate vaccines derived from individual serotype M. catarrhalis only showed partial protection coverage. A vaccine combining LOS conjugates of two or three serotypes might provide a broader protection.MethodsMice were immunized intranasally with the combined conjugates consisting of LOS from serotype A and B or serotype A, B, and C followed by challenge with different M. catarrhalis strains of three serotypes. Mouse lungs, nasal washes, and sera were collected after each challenge for bacterial counts, histological evaluation, cytokine profiles, antibody level and binding activity determinations.ResultsIntranasal administration of the combined LOS conjugates not only enhanced pulmonary bacterial clearance of all three serotypes of M. catarrhalis strains in vaccinated mice, but also elevated serotype-specific anti-LOS immunoglobulin (Ig)A and IgG titers in nasal wash and serum respectively. Mice vaccinated with the combined LOS conjugates also showed increased interferon (IFN)-γ, interleukin (IL)-12, and IL-4 in the lungs after challenges. Compared to the control group, mice immunized with the combined LOS conjugates also showed reduced lung inflammation after M. catarrhalis infections. The hyperimmune sera induced by the combined conjugates exhibited a broad cross-reactivity toward all three serotypes of M. catarrhalis under transmission electron microscopy.ConclusionsThe combined vaccine of serotype A and B LOS conjugates provides protection against most M. catarrhalis strains by eliciting humoral and cellular immune responses.

show abstract

“…Frick et al (20) and Humlicek et al (26) found that adherence of nontypeable H. influenzae to respiratory epithelial cells rapidly induced ICAM-1 expression, a process that they hypothesized would facilitate the recruitment of neutrophils to sites of nontypeable H. influenzae infection. Xie and Gu demonstrated that leukocyte recruitment mediated by enhanced ICAM-1 levels after M. catarrhalis infection may also result in increased bacterial adhesion to the respiratory tract (52). In the current study, although there is no direct evidence to illustrate that the enhanced ICAM-1 level has promoted neutrophil recruitment to the middle ear, the literature and the fact that the elevation of serum sICAM-1 levels in children with AOM positive for bacteria in MEF suggest that the intercellular adhesion molecules are upregulated during middle ear inflammation and that the increased ICAM-1 levels may contribute to innate immune responses through increasing leukocyte recruitment to the middle ear.…”

Section: Discussionmentioning

confidence: 99%

“…It is well documented that ICAM-1 is endogenously expressed on various cell types and makes possible reversible adhesion and signal transduction between cells, processes critical to T-cell development. Increased levels of ICAM-1 promote cell-cell interactions, playing a critical role in leukocyte recruitment and leading to prolonged and, sometimes, excessive inflammation (52).…”

Section: Discussionmentioning

confidence: 99%

Serum Intercellular Adhesion Molecule 1 Variations in Young Children with Acute Otitis Media

Liu

Casey

Pichichero

2010

Clin Vaccine Immunol

View full text Add to dashboard Cite

Acute otitis media (AOM) is an inflammatory reaction in the middle ear, most often occurring in young children. Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis are the most common bacteria isolated. Intercellular adhesion molecule 1 (ICAM-1) is involved in the innate immune response to infection by microorganisms, in effective antigen presentation, and in subsequent T-cell activation. Here we prospectively studied levels of serum soluble ICAM-1 (sICAM-1) before, at the time of, and after antimicrobial treatment of AOM in a group of 138 children ages 6 to 30 months. Middle ear fluids were collected by tympanocentesis to identify otopathogens. We found that (i) serum levels of sICAM-1 were significantly higher in S. pneumoniae-, nontypeable H. influenzae-, and M. catarrhalis-infected children than in well children (P < 0.001), confirming that a systemic inflammatory response occurs during AOM; (ii) sICAM-1 levels varied from no elevation (110 ng/ml) to elevation to high levels (maximum, 1,470 ng/ml) among children with AOM; (iii) in paired samples, sICAM-1 levels increased 4-to 20-fold when children developed AOM compared to their sICAM-1 levels before infection; and (iv) the level of sICAM-1 returned to the pre-AOM level at the convalescent stage of AOM after successful antimicrobial therapy. We conclude that AOM often causes a systemic inflammatory reaction, as measured by elevation of the serum sICAM-1 level, and that a high variability in sICAM-1 responses occurs with the presence of otopathogens during AOM.Acute otitis media (AOM) is defined by the presence of middle ear effusion (MEE) with acute onset of symptoms of inflammation of the middle ear. Although more than half of patients who develop AOM have fever (14), the condition is considered a localized, mucosal infection. Currently, AOM is regarded as relatively benign due to spontaneous resolution of the infection in a majority of patients (42). The complications and sequelae of bacterial systemic invasion from the middle ear, including mastoiditis, brain abscess, and meningitis, are sufficiently rare that they have recently been considered less consequential in comparison to the consequences from the costs of antimicrobial treatment and overtreatment (2).The cause and pathogenesis of otitis media are multifactorial, involving viral and bacterial infections. The most frequently isolated bacteria in AOM are Streptococcus pneumoniae (20 to 55% of cases), nontypeable Haemophilus influenzae (15 to 40%), and Moraxella catarrhalis (10 to 25%) (12,25,29). When bacteria gain entry into the middle ear space, they damage the middle ear mucosa directly by releasing toxins and indirectly by provoking both specific immunological and general inflammatory responses in the host. A prominent feature of the host response is an influx of inflammatory cells into the middle ear.The migration of leukocytes into sites of inflammation is mediated by numerous factors, including intercellular adhesion molecule 1 (ICAM-1; CD54). ICAM-1 is a m...

show abstract

Moraxella catarrhalis lipooligosaccharide selectively upregulates ICAM-1 expression on human monocytes and stimulates adjacent naïve monocytes to produce TNF-α through cellular cross-talk

Cited by 26 publications

References 52 publications

Bacterium-Generated Nitric Oxide Hijacks Host Tumor Necrosis Factor Alpha Signaling and Modulates the Host Cell Cycle In Vitro

Bacterium-Generated Nitric Oxide Hijacks Host Tumor Necrosis Factor Alpha Signaling and Modulates the Host Cell Cycle In Vitro

Intranasal Immunization of the Combined Lipooligosaccharide Conjugates Protects Mice from the Challenges with Three Serotypes of Moraxella catarrhalis

Serum Intercellular Adhesion Molecule 1 Variations in Young Children with Acute Otitis Media

Contact Info

Product

Resources

About