Mucosal immune response to specific outer membrane proteins of Moraxella catarrhalis in young children

Meier, Patricia Stutzmann; Freiburghaus, Simone; Martín, Andrea P.; Heiniger, Nadja; Troller, Rolf; Aebi, Christoph

doi:10.1097/01.inf.0000054827.86683.bd

Cited by 36 publications

(30 citation statements)

References 46 publications

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“…These virulence genes encode OMPs that play an important role in bacterial adherence to human epithelia and complement resistance, as well as being immunogenic (Helminen et al, 1994(Helminen et al, , 1995Meier et al, 2003). This finding suggests that equilibrium has been reached with respect to virulence gene distribution in global M. catarrhalis isolates, as local geographical factors do not appear to generate significant differences in virulence gene prevalence.…”

Section: Population Dynamics Ofmentioning

confidence: 49%

Colonization of healthy children by Moraxella catarrhalis is characterized by genotype heterogeneity, virulence gene diversity and co-colonization with Haemophilus influenzae

et al. 2011

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The colonization dynamics of Moraxella catarrhalis were studied in a population comprising 1079 healthy children living in Rotterdam, The Netherlands (the Generation R Focus cohort). A total of 2751 nasal swabs were obtained during four clinic visits timed to take place at 1.5, 6, 14 and 24 months of age, yielding a total of 709 M. catarrhalis and 621 Haemophilus influenzae isolates. Between January 2004 and December 2006, approximate but regular 6-monthly cycles of colonization were observed, with peak colonization incidences occurring in the autumn/winter for M. catarrhalis, and winter/spring for H. influenzae. Co-colonization was significantly more likely than single-species colonization with either M. catarrhalis or H. influenzae, with genotypic analysis revealing no clonality for co-colonizing or single colonizers of either bacterial species. This finding is especially relevant considering the recent discovery of the importance of H. influenzae-M. catarrhalis quorum sensing in biofilm formation and host clearance. Bacterial genotype heterogeneity was maintained over the 3-year period of the study, even within this relatively localized geographical region, and there was no association of genotypes with either season or year of isolation. Furthermore, chronological and genotypic diversity in three immunologically important M. catarrhalis virulence genes (uspA1, uspA2 and hag/mid ) was also observed. This study indicates that genotypic variation is a key factor contributing to the success of M. catarrhalis colonization of healthy children in the first years of life. Furthermore, variation in immunologically relevant virulence genes within colonizing populations, and even within genotypically identical M. catarrhalis isolates, may be a result of immune evasion by this pathogen. Finally, the factors facilitating M. catarrhalis and H. influenzae co-colonization need to be further investigated. INTRODUCTIONMoraxella catarrhalis is part of the normal bacterial flora in the nasopharynx of children, although over the past two decades, it has emerged as a significant bacterial pathogen and not simply a commensal colonizer (Verduin et al., 2002). Studies have shown that the bacterium rapidly colonizes the nasopharynx soon after birth and that the carriage rate of M. catarrhalis in healthy children varies between 7 and 36 % (Verhaegh et al., 2010). However, in children with upper respiratory tract infections (URTI), including acute otitis media (AOM), the carriage rate increases to approximately 50 % (Berner et al., 1996;Konno et al., 2006;Pettigrew et al., 2008). Otitis media itself is a particularly important URTI during early Abbreviations: AOM, acute otitis media; CEACAM, carcinoembryonic antigen-related cell adhesion molecule; LOS, lipooligosaccharide; MLST, multilocus sequence typing; OMP, outer-membrane protein; OR, odds ratio; OMV, outer-membrane vesicle; URTI, upper respiratory tract infection. childhood and the primary reason for children to visit a physician (Freid et al., 1998;Plasschaert et al., 2006). Furt...

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Section: Population Dynamics Ofmentioning

confidence: 49%

Colonization of healthy children by Moraxella catarrhalis is characterized by genotype heterogeneity, virulence gene diversity and co-colonization with Haemophilus influenzae

et al. 2011

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“…To determine the identities of some of the antigens to which human IgA antibodies were directed, a series of isogenic knockout mutants of M. catarrhalis were studied in immunoblot assays with purified IgA from postclearance sputum samples. The characteristics of the mutants are noted in Table 1 and have been described previously (10,11,14). Purified outer membranes of the homologous infecting strains, each of the knockout mutants, and the isogenic parent strain used to make the mutants were subjected to immunoblot assay with purified IgA.…”

Section: Resultsmentioning

confidence: 99%

“…The characteristics of M. catarrhalis O35E and its isogenic knockout mutants are shown in Table 1 and were described previously (10,11,14).…”

Section: Copd Studymentioning

confidence: 99%

Antigenic Specificity of the Mucosal Antibody Response to Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease

et al. 2005

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Moraxella catarrhalis is an important human mucosal pathogen causing otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Little is known about the mucosal antibody response to M. catarrhalis in adults with COPD. In this study, 10 pairs of wellcharacterized sputum supernatant samples from adults with COPD who had acquired and subsequently cleared M. catarrhalis from their respiratory tracts were studied in detail in an effort to begin to elucidate potentially protective immune responses. Flow cytometry analysis was used to study the distribution of immunoglobulin isotypes in paired preacquisition and postclearance sputum samples. The results showed that immunoglobulin A (IgA) is the predominant M. catarrhalis-specific immunoglobulin isotype and that the sputum IgA contains a secretory component, indicating that it is locally produced at the mucosal site. Chronic obstructive pulmonary disease (COPD) is a debilitating disease that is the fourth most common cause of death in the United States (2, 4). Bacteria play several potential roles in the course and pathogenesis of the disease (20). Selected bacteria colonize the lower airways of adults with COPD and release potent inflammatory molecules that contribute to the airway inflammation that is a hallmark of COPD (6,7,13,21,22). Patients with COPD acquire and clear bacteria from the respiratory tract continuously. Little is known about the immune responses that mediate this turnover of bacteria. The course of COPD is characterized by intermittent episodes of worsening of symptoms, known as exacerbations. It is estimated that approximately half of the exacerbations are caused by bacterial infection (20,23,24). Nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae are the most frequent bacterial causes of exacerbations of COPD (19,20).Studies involving the molecular typing of isolates recovered from sputum samples collected prospectively have begun to elucidate the dynamics of colonization and infection by M. catarrhalis in the setting of COPD (15). M. catarrhalis likely causes approximately 10% of exacerbations of COPD, accounting for approximately 2 to 4 million episodes annually. When adults with COPD acquire M. catarrhalis, the organism is cleared efficiently from the respiratory tract after a relatively short duration of carriage (median time, 34 days). Patients then develop strain-specific protection against reacquisition of the same strain (15). This observation that humans develop apparent protective responses to M. catarrhalis after clearing it from the respiratory tract provides the opportunity to begin to understand protective immune responses. The majority of patients develop serum immunoglobulin G (IgG) and/or sputum IgA responses to their homologous infecting isolate of M. catarrhalis, as demonstrated by whole-cell enzyme-linked immunosorbent assay and flow cytometry assays (3, 15). Further analysis of serum immunoglobulins in this cohort has revealed...

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“…Hag (and indeed UspA1) have been previously shown to be immunogenic in children and adults (Meier et al, 2003;Murphy et al, 2005a, b, c). It is, however, possible that UspA1 and Hag expression in vivo may differ from that observed in vitro, meaning that further research is necessary to verify the clinical significance of our observations.…”

Section: Discussionmentioning

confidence: 99%

“…All of these vaccine candidates have been associated with the production of antibody (Bakri et al, 2002;Faden, 1995;Meier et al, 2003;Murphy et al, 2003Murphy et al, , 2005b, although little is known about the frequency and expression of the corresponding genes in global isolates recovered from children and adults.…”

Section: Introductionmentioning

confidence: 99%

Age-related genotypic and phenotypic differences in Moraxella catarrhalis isolates from children and adults presenting with respiratory disease in 2001–2002

et al. 2008

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Moraxella catarrhalis is generally associated with upper respiratory tract infections in children and lower respiratory tract infections in adults. However, little is known regarding the population biology of isolates infecting these two age groups. To address this, a population-screening strategy was employed to investigate 195 worldwide M. catarrhalis isolates cultured from children (,5 years of age) and adults (.20 years of age) presenting with respiratory disease in the years [2001][2002]. Parameters compared included: genotype analysis; autoagglutination/biofilmforming ability; serum resistance; uspA1, uspA2, uspA2H, hag and mcaP incidence; copB/LOS/ ompCD/16S rRNA types; and UspA1/Hag expression. A significant difference in biofilm formation (P50.002), but not in autoagglutination or serum resistance, was observed, as well as significant differences in the incidence of uspA2-and uspA2H-positive isolates, and the distribution of lipooligosaccharide (LOS) types (P,0.0001 and P50.01, respectively). Further, a significant decrease in the incidence of Hag expression (for isolates possessing the hag gene) was observed in adult isolates (P50.001). Both uspA2H and LOS type B were associated with 16S rRNA type 1 isolates only, and two surrogate markers (copB and ompCD PCR RFLP types) for the two major M. catarrhalis 16S rRNA genetic lineages were identified. In conclusion, there are significant differences in phenotype and gene incidence between M. catarrhalis isolates from children and adults presenting with respiratory disease, possibly as a result of immune evasion in the adult age group. Our results should also be useful in the choice of effective vaccine candidates against M. catarrhalis.

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Mucosal immune response to specific outer membrane proteins of Moraxella catarrhalis in young children

Abstract: colonization occurring in early infancy is associated with a consistent mucosal immune response directed against the UspA proteins, Hag and other OMP. The data suggest that several M. catarrhalis OMP are immunogens of the nasopharyngeal mucosal immune system of infants.

Cited by 36 publications

References 46 publications

Colonization of healthy children by Moraxella catarrhalis is characterized by genotype heterogeneity, virulence gene diversity and co-colonization with Haemophilus influenzae

Colonization of healthy children by Moraxella catarrhalis is characterized by genotype heterogeneity, virulence gene diversity and co-colonization with Haemophilus influenzae

Antigenic Specificity of the Mucosal Antibody Response to Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease

Age-related genotypic and phenotypic differences in Moraxella catarrhalis isolates from children and adults presenting with respiratory disease in 2001–2002

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