Inhibition of neutrophil lysosome-phagosome fusion associated with influenza virus infection in vitro. Role in depressed bactericidal activity.

Abramson, Jon S.; Lewis, Jon C.; Lyles, Douglas S.; Heller, Kelley A.; Mills, Elaine L.; Bass, David

doi:10.1172/jci110580

Cited by 87 publications

(42 citation statements)

References 16 publications

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“…In vitro studies have shown that influenza virus is able to cause apoptosis in neutrophils (9) and inhibit phagocytic and chemotaxic function of macrophages (19,26). Other studies have observed a decrease in chemotactic activity of neutrophils at the time of secondary infection in an in vitro model (2). In our synergy model, however, we did not observe overt signs of neutropenia.…”

Section: Discussioncontrasting

confidence: 70%

Filamentous Influenza A Virus Infection Predisposes Mice to Fatal Septicemia following Superinfection with Streptococcus pneumoniae Serotype 3

et al. 2007

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Previous studies have demonstrated that animals exposed to Streptococcus pneumoniae while recovering from influenza A virus infection exhibit exacerbated disease symptoms. However, many of the current animal models exploring dual viral and bacterial synergistic exacerbations of respiratory disease have utilized mouse-adapted influenza virus and strains of Streptococcus pneumoniae that in themselves are highly lethal to mice. Here we describe a mouse model of bacterial superinfection in which a mild, self-limiting influenza virus infection is followed by mild, self-limiting superinfection with S. pneumoniae serotype 3. S. pneumoniae superinfection results in rapid dissemination of the bacterium from the respiratory tract and systemic spread to all major organs of the mice, resulting in fatal septicemia. This phenomenon in mice was observed in superinfected animals undergoing an active viral infection as well as in mice that had completely cleared the virus 7 to 8 days prior to superinfection. Neutrophils were the predominant cellular inflammatory infiltrate in the lungs of superinfected mice compared to singly infected animals. Among other cytokines and chemokines, the neutrophil activator granulocyte colony-stimulating factor (G-CSF) was found to be significantly overexpressed in the spleens, lungs, and brains of superinfected animals. High G-CSF protein levels were observed in sera and lung lavage fluid from superinfected animals, suggesting that G-CSF is a major contributor to synergistic exacerbation of disease leading to fatal septicemia.

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Section: Discussioncontrasting

confidence: 70%

Filamentous Influenza A Virus Infection Predisposes Mice to Fatal Septicemia following Superinfection with Streptococcus pneumoniae Serotype 3

et al. 2007

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“…Like the interactions of oral actinomyces and streptococci, the interaction of IAV with PMNs stimulates the respiratory burst (28), degranulation (21), and phagocytosis (2). Significantly, IAV also causes deactivation of various PMN metabolic and bactericidal activities, and this effect may be associated with increased susceptibility of IAV patients to secondary bacterial infections (1,2). Activation and deactivation appear to be triggered, at least in part, by the multivalent interaction of virus particles with cell surface leukosialin as both effects can also be induced by cross-linking leukosialin with specific antibodies or sialic acid-binding lectins such as LFA (8,19).…”

Section: Discussionmentioning

confidence: 99%

Identification of Polymorphonuclear Leukocyte and HL-60 Cell Receptors for Adhesins ofStreptococcus gordoniiandActinomyces naeslundii

2000

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Interactions of oral streptococci and actinomyces with polymorphonuclear leukocytes (PMNs), mediated by sialic acid-and Gal/GalNAc-reactive adhesins, respectively, result in activation of the PMNs and thereby may contribute to the initiation of oral inflammation. Sialidase treatment of PMNs or HL-60 cells abolished adhesion of Streptococcus gordonii but was required for adhesion of Actinomyces naeslundii. The same effects of sialidase were noted for adhesion of these bacteria to a major 150-kDa surface glycoprotein of either PMNs or undifferentiated HL-60 cells and to a 130-kDa surface glycoprotein of differentiated HL-60 cells. These glycoproteins were both identified as leukosialin (CD43) by immunoprecipitation with a specific monoclonal antibody (MAb). Adhesion of streptococci and actinomyces to a 200-kDa minor PMN surface glycoprotein was also detected by bacterial overlay of untreated and sialidase-treated nitrocellulose transfers, respectively. This glycoprotein was identified as leukocyte common antigen (CD45) by immunoprecipitation with a specific MAb. CD43 and CD45 both possess extracellular mucinlike domains in addition to intracellular domains that are implicated in signal transduction. Consequently, the interactions of streptococci and actinomyces with the mucinlike domains of these mammalian cell surface glycoproteins result not only in adhesion but, in addition, may represent the initial step in PMN activation by these bacteria.

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“…Earlier studies have reported impairment in macrophage and neutrophil responses following influenza infection (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), but the molecular pathways underlying these defects have not been fully elucidated. Although various factors, including upregulation of platelet-activating factor receptor and the antiinflammatory cytokine IL-10 during influenza infection, have been implicated in promoting postinfluenza secondary pneumococcal pneumonia, attempts at modifying these factors have had limited effects on bacterial clearance (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice

Shahangian¹,

Chow²,

Tian³

et al. 2009

J. Clin. Invest.

443

510

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Influenza-related complications continue to be a major cause of mortality worldwide. Due to unclear mechanisms, a substantial number of influenza-related deaths result from bacterial superinfections, particularly secondary pneumococcal pneumonia. Here, we report what we believe to be a novel mechanism by which influenza-induced type I IFNs sensitize hosts to secondary bacterial infections. Influenza-infected mice deficient for type I IFN-α/β receptor signaling (Ifnar -/-mice) had improved survival and clearance of secondary Streptococcus pneumoniae infection from the lungs and blood, as compared with similarly infected wild-type animals. The less effective response in wild-type mice seemed to be attributable to impaired production of neutrophil chemoattractants KC (also known as Cxcl1) and Mip2 (also known as Cxcl2) following secondary challenge with S. pneumoniae. This resulted in inadequate neutrophil responses during the early phase of host defense against secondary bacterial infection. Indeed, influenza-infected wild-type mice cleared secondary pneumococcal pneumonia after pulmonary administration of exogenous KC and Mip2, whereas neutralization of Cxcr2, the common receptor for KC and Mip2, reversed the protective phenotype observed in Ifnar -/-mice. These data may underscore the importance of the type I IFN inhibitory pathway on CXC chemokine production. Collectively, these findings highlight what we believe to be a novel mechanism by which the antiviral response to influenza sensitizes hosts to secondary bacterial pneumonia.

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Inhibition of neutrophil lysosome-phagosome fusion associated with influenza virus infection in vitro. Role in depressed bactericidal activity.

Cited by 87 publications

References 16 publications

Filamentous Influenza A Virus Infection Predisposes Mice to Fatal Septicemia following Superinfection with Streptococcus pneumoniae Serotype 3

Filamentous Influenza A Virus Infection Predisposes Mice to Fatal Septicemia following Superinfection with Streptococcus pneumoniae Serotype 3

Identification of Polymorphonuclear Leukocyte and HL-60 Cell Receptors for Adhesins ofStreptococcus gordoniiandActinomyces naeslundii

Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice

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