Virus-induced secondary bacterial infection: a concise review

Hendaus, Mohamed A; Jomha, Fatima A; Alhammadi, Ahmed H

The epithelium ( Figure 2) is usually covered by a layer of mucus that functions as a boundary. 16 Mucins, which are charged glycoproteins, are the main components of mucus. 17, 18 MUC5AC and MUC5B are the most common mucins in the human sputum, and they assist the innate immune system through their anti-inflammatory and antiviral properties. 19, 20 In addition, they facilitate trapping and clearance of viruses; however, overproduction of those mucins might have a paradoxical effect. 18, 19 The airway epithelium not only functions as a physical barrier but also recognizes microorganisms through pattern recognition receptors such as Toll-like receptors (TLRs), 18 nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and retinoic acid-inducible gene (RIG)like helicases. 21, 22 TLRs are single, noncatalytic, membrane-spanning receptor proteins used by the innate immune system. 23 Respiratory viruses collaborate with TLR lanes, leading to extended bacterial load in the lungs. 21, 24 In comparison, NLRs and RIG-like helicases activate innate immune responses through cytosolic sensing of viral and bacterial components. 22, 25 Nod1 and Nod2, which are family members of NLRs, are induced by molecules synthesized during the production and/or degradation of bacterial peptidoglycan. [26] [27] [28] [29] In addition, many epithelial cells express the classical antiviral interferons (INFs), especially IFN-α and IFN-β. 30, 31 Moreover, the respiratory virus-infected epithelia facilitates the attraction of inflammatory cells, including natural killer cells, neutrophils, macrophages, and eosinophils from the bloodstream into the infected site. 32 Finally, the airway epithelium consists of many molecules including intercellular adhesion molecule 1 (ICAM-1), carcinoembryonic antigen-related cellular adhesion 1 (CEACAM-1), and platelet-activating factor receptor (PAF-r). 33 Viruses have an effect in modulating these receptors, leading to an increase risk of bacterial adherence; for example, rhinovirus upregulates the expression of PAF-r, leading to the binding of S. pneumoniae to bronchial epithelial cells. 34