Defect in intracellular killing of Staphylococcus aureus within alveolar macrophages in Sendai virus-infected murine lungs.

Abstract

A B S T R A C T Bacterial multiplication associated with virus infections is related to defects in in situ bactericidal (phagocytic) mechanisms of the lung. To determine whether the phagocytic defect was in bacterial ingestion and/or intracellular digestion, mice were infected with a sublethal dose of aerosolized Sendai virus and challenged 7 days later with a finely dispersed aerosol of Staphylococcuts aureus. Groups of uninfected and virus-infected mice were sacrificed at 0, 6, 12, and 24 h after challenge, the lungs were perfused with formalin in situ, and the intra-or extracellular location of the bacteria was determined histologically. At 0 h, 49% and 51% of the staphylococci had an intracellular location in virus and nonvirus-infected lungs, respectively. With time, decreasing numbers of staphylococci were observed within the phagocytic cells of nonvirus-infected lungs, mostly as single organisms or in small clusters of less than four. Ill contrast, in focal area of virus-infected lungs, increasing numbers of phagocytic cells showed clumps of more than 25 bacteria/cell. These data demonstrate that virus-infected suppression of pulmonary antibacterial activity against S. aureus is related primarily to defects in intracellular processing mechanisms.

Parainfluenza virus type-3 infection attenuates the respiratory effects of antigen challenge in sensitized guinea pigs

“…PI-3 virus can infect alveolar macrophages [10] and a recent study reports bovine PI-3 virus selectively depletes a calcium-independent phospholipid-dependent protein kinase C and inhibits superoxide anion generation in bovine alveolar macrophages [11]. This is consistent with the inability of PI-1 virus to limit the ability of mouse alveolar macrophages to kill Staphylococcus aureus [12]. It has also been proposed that the failure of infected macrophages to provide proliferation signals to lymphocytes and/or destruction of lymphocytes by cytotoxic products could explain the immunosuppressive effects of viruses [13].…”

Staphylococcus aureus Strain USA300 Perturbs Acquisition of Lysosomal Enzymes and Requires Phagosomal Acidification for Survival inside Macrophages

“…Although most evidence of S. aureus survival inside host cells is derived from experiments conducted in nonphagocytes, a growing number of reports show that some strains of S. aureus also survive within professional phagocytes such as macrophages and neutrophils (9,11,13,14,18,19). However, neutrophils are unlikely to contribute to S. aureus dissemination and persistent infections since they are short-lived cells and because S. aureus induces rapid neutrophil cell death following phagocytosis (20,21).…”

“…In contrast to neutrophils, macrophages are better suited as vehicles for persistence and dissemination because they are long-lived migratory cells (22) that, if carrying live S. aureus, could spread the bacterium from initial sites of infection to systemic circulation and deeper tissues (23). Indeed, macrophages are rapidly recruited to sites of S. aureus infection, where they internalize the bacteria within minutes of infection (18,24). S. aureus can survive for days inside macrophages (13) and even prolong macrophage survival by inducing antiapoptotic factors during early stages of infection (25).…”

Dysregulated Macrophage-Inflammatory Protein-2 Expression Drives Illness in Bacterial Superinfection of Influenza

“…Although neutrophils are required for B. parapertussis clearance (27), it is important to note that influenza infection may impair neutrophil function to the extent that even partial depletion of neutrophils from influenza-infected mice does not further damage antibacterial host defense (48). In addition, AMs are second only to respiratory epithelial cells as a target for influenza, and direct viral infection may further compromise their antibacterial function, as has been reported in other models (20,24). Moreover, the presence of neutrophils, whether functional or not, in the influenza-infected airway at the time of bacterial challenge is a key difference between bacterial-only and heterologously infected mice.…”

“…In epithelial cells that escape direct lysis, influenza and other viruses may then increase the expression of receptors to which bacteria adhere (16) and impair ciliary function, reducing early mucocilliary clearance of bacteria (17,18). Additionally, viral insult may impair macrophage responsiveness to bacterial TLR ligands by reducing NF-kB activity (19) and reduce macrophage antibacterial function (20). Viral induction of type I IFNs may then compromise innate antibacterial immunity by inducing granulocyte apoptosis (21) and reducing the production of inflammatory chemokines (22).…”