Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms

Figures & data

Table 1. Virulence factors involved in molecular mechanisms of interactions between Staphylococcus aureus and non-influenza respiratory viruses.

Virulence factors	Cellular target	Effects	Synergism	References
Staphylococcus aureus
SEA/SEB	Unknown	Increase of IL-1β, IL-6 and IL-8 secretion	Increase of ICAM-1 expression Enhancement of rhinovirus replication	[53,83–85]
LTA	Unknown	Increase of IL-6, IL-12/IL-23 and IFN-γ secretion	Increase of susceptibility to coronavirus	[98]
Human rhinovirus
Capsid	Membrane TLR2	NFκB activation Increase of IL-6, IL-8, INFβ and IFN-γ secretion	Increase of cFn and ICAM-1 expression Increase of S. aureus adhesion and internalization to/in host cells	[48,51–56]
ssRNA	Endosomal TLR7/8
	Cytoplasmic RIG-I	Increase of IFN-β, IFN-γ, RANTES, IL-8, IP-10 and ENA78 secretion
dsRNA	Cytoplasmic MDA5
	Endosomal TLR3	RIG-I and MDA5 upregulation NFκB activation Increase of IL-6, IL-8, INF-β and IFN-γ secretion
	Unknown	Rac1 activation NOX1 production Stimulation of ROS generation	Loss of ZO-1 tight junctions Induce S. aureus invasion of the epithelium	[78,81]
Respiratory Syncytial Virus
Viral envelope	Membrane TLR2	NFκB activation Increase of pro-inflammatory cytokine secretion IRFs activation Increase of type I IFNs secretion	Alteration of neutrophil recruitment Inhibition of B cells response Decrease of S. aureus clearance	[87,90,93,94,99]
Viral F protein	Membrane TLR4
ssRNA	Endosomal TLR3
	Cytoplasmic RIG-I
	Cytoplasmic Nod2
dsRNA	Endosomal TLR7
	Cytoplasmic MDA5
Unknown	NKG2D	Increase of IFN-γ secretion
Unknown	Unknown	Increase of Lewis blood group antigen expression	Increase of toxin-producing S. aureus binding to epithelial cells	[88,89,91]

Figure 1. Mechanisms of bi-directional synergism between Staphylococcus aureus and human rhinovirus in non-professional phagocytic epithelial cells. S. aureus increases HRV replication via SEA and SEB. HRV increases adhesion and internalization of S. aureus in both HRV-infected and uninfected cells through increased release of IL-1β, IL-6 and IL-8 and subsequent increase of ICAM-1 and cFn expression via NFkB activation. HRV inhibits ZO-1 tight junctions favoring S. aureus invasion of the epithelium.

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