FIGURE 2.

Co-infection with oral microbes strengths the pathogenicity of respiratory pathogens. Usually, respiratory pathogen infection (black arrow) could induce the Th cells to produce cytokines, then lead to the differentiation, activation and recruitment of effector lymphocytes, neutrophils and macrophages. These immune cells not only bring about inflammation, but also activate the death receptor apoptotic pathway and finally lead to apoptosis. Once oral microbes (including oral streptococci, P. gingivalis, F. nucleatum and A. actinomycetemcomitans, Prevotella intermedia, C. albicans) inhaled into airways co-infect respiratory epithelium with respiratory pathogens (red arrow), the levels of multiple cytokines are elevated including TNF-α, IL-1ß, IL-6, as well as those signaling pathway related with apoptosis of respiratory epithelial cells. Besides, some oral microbes can promote the virulence of respiratory pathogens, for example, via increasing the virulence factor production or forming pathogenic partnerships. As a result, aggravated inflammation and expanded apoptosis is observed.