Pulmonary Collectins Modulate Strain-Specific Influenza A Virus Infection and Host Responses

Hawgood, Samuel; Brown, Cynthia L.; Edmondson, Jess; Stumbaugh, Amber; Allen, Lennell; Goerke, Jon; Clark, Howard; Poulain, Francis R

doi:10.1128/jvi.78.16.8565-8572.2004

Cited by 103 publications

(119 citation statements)

References 39 publications

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“…Levels of SP-D recovered from the airways by lavage increase significantly following infection of mice with influenza virus (3, 9 -11), and SP-D Ϫ/Ϫ mice exhibit enhanced viral replication and illness (9,11). SP-A Ϫ/Ϫ mice also display enhanced susceptibility to influenza infections in some studies (9,10), but not others (12); however, the effect is less pronounced than that observed in SP-D Ϫ/Ϫ mice.…”

mentioning

confidence: 74%

“…PTX3 and SP-D may play distinct but cooperative roles in innate host defense against H3N2 subtype viruses; PTX3 sensitivity was a feature of early virus strains (1968 -1975) whereas SP-D sensitivity was a feature of later (1977)(1978)(1979)(1980)(1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993) and currently circulating strains. Studies using SP-D Ϫ/Ϫ mice (9,11) have demonstrated the importance of SP-D in limiting disease in mice infected with late H3N2 subtype viruses that we have shown to be resistant to PTX3. Together, innate inhibitors may play a cooperative role in limiting initial virus replication and spread but the predominant inhibitor acting to limit virus growth may be different for particular virus strains.…”

Section: Discussionmentioning

confidence: 99%

“…Both surfactant protein-A (SP-A) and SP-D mediate a range of activities against influenza virus, including inhibition of hemagglutination, virus neutralization, virus aggregation, and opsonizaton of the virus for interaction with neutrophils (2)(3)(4)(5)(6)(7)(8), with SP-D acting as a more potent inhibitor than SP-A in vitro (4). Levels of SP-D recovered from the airways by lavage increase significantly following infection of mice with influenza virus (3, 9 -11), and SP-D Ϫ/Ϫ mice exhibit enhanced viral replication and illness (9,11). SP-A Ϫ/Ϫ mice also display enhanced susceptibility to influenza infections in some studies (9,10), but not others (12); however, the effect is less pronounced than that observed in SP-D Ϫ/Ϫ mice.…”

mentioning

confidence: 99%

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Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Reading

Bozza

Gilbertson

et al. 2008

The Journal of Immunology

179

212

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Proteins of the innate immune system can act as natural inhibitors of influenza virus, limiting growth and spread of the virus in the early stages of infection before the induction of adaptive immune responses. In this study, we identify the long pentraxin PTX3 as a potent innate inhibitor of influenza viruses both in vitro and in vivo. Human and murine PTX3 bound to influenza virus and mediated a range of antiviral activities, including inhibition of hemagglutination, neutralization of virus infectivity and inhibition of viral neuraminidase. Antiviral activity was associated with binding of the viral hemagglutinin glycoprotein to sialylated ligands present on PTX3. Using a mouse model we found PTX3 to be rapidly induced following influenza infection and that PTX3−/− mice were more susceptible than wild-type mice to infection by PTX3-sensitive virus strains. Therapeutic treatment of mice with human PTX3 promoted survival and reduced viral load in the lungs following infection with PTX3-sensitive, but not PTX3-resistant, influenza viruses. Together, these studies describe a novel antiviral role for PTX3 in early host defense against influenza infections both in vitro and in vivo and describe the therapeutic potential of PTX3 in ameliorating disease during influenza infection.

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confidence: 74%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Reading

Bozza

Gilbertson

et al. 2008

The Journal of Immunology

179

212

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show abstract

“…The pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D), are pulmonary epithelium-derived host defense proteins that have been previously reported to bind to HA and opsonize and agglutinate IAV (19)(20)(21)(22)(23)(24). Keratinocyte growth factor (KGF), a potent epithelial mitogen and differentiation factor, has been shown to increase pulmonary collectin expression, promote epithelial Significance Influenza is a recurring global health threat that preferentially targets vulnerable groups such as the very young, the pregnant, the elderly, and the infirm.…”

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confidence: 99%

Mitogenic stimulation accelerates influenza-induced mortality by increasing susceptibility of alveolar type II cells to infection

Nikolaidis

Noel²,

Pitstick

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Development of pneumonia is the most lethal consequence of influenza, increasing mortality more than 50-fold compared with uncomplicated infection. The spread of viral infection from conducting airways to the alveolar epithelium is therefore a pivotal event in influenza pathogenesis. We found that mitogenic stimulation with keratinocyte growth factor (KGF) markedly accelerated mortality after infectious challenge with influenza A virus (IAV). Coadministration of KGF with IAV markedly accelerated the spread of viral infection from the airways to alveoli compared with challenge with IAV alone, based on spatial and temporal analyses of viral nucleoprotein staining of lung tissue sections and dissociated lung cells. To better define the temporal relationship between KGF administration and susceptibility to IAV infection in vivo, we administered KGF 120, 48, 24, and 0 h before intrapulmonary IAV challenge and assessed the percentages of proliferating and IAV-infected, alveolar type II (AECII) cells in dispersed lung cell populations. Peak AECII infectivity coincided with the timing of KGF administration that also induced peak AECII proliferation. AECII from mice that were given intrapulmonary KGF before isolation and then infected with IAV ex vivo exhibited the same temporal pattern of proliferation and infectious susceptibility. KGF-induced increases in mortality, AECII proliferation, and enhanced IAV susceptibility were all reversed by pretreatment of the animals with the mTOR inhibitor rapamycin before mitogenic stimulation. Taken together, these data suggest mTOR signalingdependent, mitogenic conditioning of AECII is a determinant of host susceptibility to infection with IAV. viral pneumonia | influenza A | alveolar epithelial type II | mitogen | mTOR

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“…Removal of SP-D from bronchoalveolar lavage (BAL) fluid significantly reduced antiviral activity (19). SP-D knockout mice exhibit greatly increased viral titers, lung inflammation, and illness after infection with IAV (26,35). SP-A knockout mice also exhibit increased viral titers and inflammation after IAV infection, although these effects are less pronounced than in SP-D knockout mice (26,34).…”

mentioning

confidence: 98%

Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus

White¹,

Crouch²,

Vesona³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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Oxidants and neutrophils contribute to lung injury during influenza A virus (IAV) infection. Surfactant protein (SP)-D plays a pivotal role in restricting IAV replication and inflammation in the first several days after infection. Despite its potent anti-inflammatory effects in vivo, preincubation of IAV with SP-D in vitro strongly increases neutrophil respiratory burst responses to the virus. Several factors are shown to modify this apparent proinflammatory effect of SP-D. Although multimeric forms of SP-D show dose-dependent augmentation of respiratory burst responses, trimeric, single-arm forms either show no effect or inhibit these responses. Furthermore, if neutrophils are preincubated with multimeric SP-D before IAV is added, oxidant responses to the virus are significantly reduced. The ability of SP-D to increase neutrophil uptake of IAV can be dissociated from enhancement of oxidant responses. Finally, several other innate immune proteins that bind to SP-D and/or IAV (i.e., SP-A, lung glycoprotein-340 or mucin) significantly reduce the ability of SP-D to promote neutrophil oxidant response. As a result, the net effect of bronchoalveolar lavage fluids is to increase neutrophil uptake of IAV while reducing the respiratory burst response to virus.

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Pulmonary Collectins Modulate Strain-Specific Influenza A Virus Infection and Host Responses

Cited by 103 publications

References 39 publications

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Mitogenic stimulation accelerates influenza-induced mortality by increasing susceptibility of alveolar type II cells to infection

Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus

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