catarrhalis. The overall presence of lactoferrin receptors in M. catarrhalis isolates suggests its important role in colonization or infection [32]. In our previous study we demonstrated that exposure of M. catarrhalis to 26°C increases the release of proinflammatory cytokine IL-8 in pharyngeal epithelial cells likely leading to the increased inflammation [10].

Thus, greater local concentrations of IL-8 would promote enhanced recruitment and influx of neutrophils that release lactoferrin from their secondary granules, which contribute to lactoferrin levels both locally and in the circulation [33, 34]. On the other hand, increased expression of M. catarrhalis lactoferrin binding proteins following cold shock would facilitate the binding

and acquisition of iron from lactoferrin to support growth of bacteria in the mucosal environment. NVP-LDE225 It has been shown that supplemental lactoferrin can enhance the virulence of meningococcal infection in mice [35]. In addition to iron acquisition, lactoferrin receptors may provide protection against anti-bacterial cationic peptides (eg, lactoferricin) and reduce complement-mediated killing. The pneumococcal surface protein PspA binds lactoferrin and protects Streptococcus pneumoniae against the antibacterial effect of lactoferricin [26]. The release of LbpB from the cell surface by a NalP protease protects Neisseria meningitidis against bactericidal antibodies [36]. Therefore, increased expression

of lactoferrin receptors and enhanced binding of 26s Proteasome structure lactoferrin on the surface of bacteria following cold shock might be associated with enhanced protection of M. catarrhalis against anti-bacterial cationic peptides and bactericidal antibodies. The level of UspA2 protein that afforded serum resistance in the bactericidal activity assay has been shown to Non-specific serine/threonine protein kinase correlate with increased binding of vitronectin [37]. Our results indicate that cold shock upregulates the UspA2 protein expression and promotes M. catarrhalis binding to vitronectin. Increased UspA2 protein expression at 26°C was not the result of higher copy number of uspA2 mRNA, indicating that post-transciptional mechanisms are involved in upregulation of this protein after cold shock [38]. Cold shock did not influence the serum resistance of O35E strain indicating that M. catarrhalis strains may need to maintain a certain threshold level of UspA2 protein necessary to evade host defenses. Most seroresistant M. catarrhalis strains express at 37°C sufficient levels of UspA2 to mediate serum resistance [37]. It is conceivable that cold shock would increase UspA2 expression and vitronectin binding in M. catarrhalis strains constitutively expressing low levels of UspA2, leading to the enhanced serum resistance. The infant population during the first year of life possesses a substantial proportion of IgD in saliva [39].