Table 2.

Known or suspected steps in the pathogenesis of secondary bacterial pneumonia

Immune Function	Viral-mediated Effect
Nasopharyngeal colonization	•Altered host microbiota, possibly in favor of more pathogenic organisms
Direct mucosal/epithelial damage	•Breakdown of mucin by viral and bacterial neuraminidase •Destruction of epithelium and exposure of basement membrane •Impairment of ciliary function
Enhanced bacterial adherence	•Cleavage of sialic acid → exposure of receptors for bacteria on mucosal surface
Alveolar macrophage response	•Decreased number of AMs after viral infection •Downregulation of MARCO (macrophage receptor with collagenous structure) receptor resulting in impaired phagocytosis of bacteria •Reduced chemokine expression and immune cell recruitment •Desensitization of Toll-like receptors → long-term immune defects
Neutrophil response	•Possible reduced recruitment to the lung •Decreased phagocytic function •Reduced production of reactive oxygen species •Impaired NETs function
Altered cytokine milieu	•Increased type I interferons → reduced macrophage and neutrophil recruitment to the lung •Increased type II interferons → impaired macrophage phagocytic function, possible viral skewing of neutrophils •Attenuated TH17 cell function and decreased IL-17 secretion → increased susceptibility to S pneumoniae, decreased production of antimicrobial peptides

Abbreviations: AMS, alveolar macrophages; IL, interleukin; NETs, neutrophil extracellular traps; T_H, T-helper.