Human lung innate immune cytokine response to adenovirus type 7

Wu, Wenxin; Booth, J. Leland; Duggan, Elizabeth S.; Patel, Krupa B.; Coggeshall, K. Mark; Metcalf, Jordan P.

doi:10.1099/vir.0.017905-0

Cited by 38 publications

(33 citation statements)

References 28 publications

(19 reference statements)

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“…Previous reports have characterized innate cytokine profiles of Ad vectors in mice (3,4,53) and in vitro (2,18,19,20,29,36,52). For example, several studies have reported that Ad35 induces higher levels of the costimulatory markers CD80 and CD40 and interferons than does Ad5 in vitro in human DC (29) as well as higher levels of IL-10 and reduced proliferation in T cells cocultured with DCs (2).…”

Section: Discussionmentioning

confidence: 99%

Vaccination with Adenovirus Serotypes 35, 26, and 48 Elicits Higher Levels of Innate Cytokine Responses than Adenovirus Serotype 5 in Rhesus Monkeys

Teigler

Iampietro

Barouch

2012

J Virol

112

126

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Adenovirus (Ad) vaccine vectors have proven highly immunogenic in multiple experimental models, but the innate immune responses induced by these vectors remain poorly characterized. Here we report innate cytokine responses to 5 different Ad vectors in 26 rhesus monkeys. Vaccination with adenovirus serotype 35 (Ad35), Ad26, and Ad48 induced substantially higher levels of antiviral (gamma interferon [IFN-γ], 10-kDa gamma interferon-induced protein [IP-10]) and proinflammatory (interleukin 1 receptor antagonist [IL-1RA], IL-6) cytokines than vaccination with Ad5 on day 1 following immunization.In vitrostudies with capsid chimeric vectors and receptor-blocking monoclonal antibodies suggested that fiber-receptor interactions, as well as other capsid components, were critical for triggering these innate responses. Moreover, multiple cell populations, including dendritic cells, monocytes/macrophages, and T lymphocytes, contributed to these innate cytokine profiles. These data demonstrate that Ad35, Ad26, and Ad48, which utilize CD46 as their primary cellular receptor, induce significantly greater innate cytokine responses than Ad5, which uses the coxsackievirus and adenovirus receptor (CAR). These differences in innate triggering result in markedly different immunologic milieus for the subsequent generation of adaptive immune responses by these vaccine vectors.

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Section: Discussionmentioning

confidence: 99%

Vaccination with Adenovirus Serotypes 35, 26, and 48 Elicits Higher Levels of Innate Cytokine Responses than Adenovirus Serotype 5 in Rhesus Monkeys

Teigler

Iampietro

Barouch

2012

J Virol

112

126

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“…Alveolar macrophages are sensors for infection and detect adenoviruses in the airway lumen 28 . On contact with viruses, they undergo rapid activation and secrete pro-inflammatory cytokines, such as IL-6, CXCL8 and TNF-α 29,30 . This boosts the antiviral response, attracts leukocytes to the site of infection and critically contributes to mounting adaptive immune responses against the virus.…”

Section: Discussionmentioning

confidence: 99%

Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells

et al. 2011

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mucosal epithelia provide strong barriers against pathogens. For instance, the outward facing apical membrane of polarized epithelial cells lacks receptors for agents, such as hepatitis C virus, herpesvirus, reovirus, poliovirus or adenovirus. In addition, macrophages eliminate pathogens from the luminal space. Here we show that human adenovirus type 5 engages an antiviral immune response to enter polarized epithelial cells. Blood-derived macrophages co-cultured apically on polarized epithelial cells facilitate epithelial infection. Infection also occurs in the absence of macrophages, if virus-conditioned macrophage-medium containing the chemotactic cytokine CXCL8 (interleukin-8), or recombinant CXCL8 are present. In polarized cells, CXCL8 activates a src-family tyrosine kinase via the apical CXCR1 and CXCR2 receptors. This activation process relocates the viral co-receptor ανβ3 integrin to the apical surface, and enables apical binding and infection with adenovirus depending on the primary adenovirus receptor CAR. This paradigm may explain how other mucosal pathogens enter epithelial cells.

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“…We have pioneered the use of human lung slices to study the pathophysiology of innate immune responses to infectious agents, including adenovirus (Ad), influenza virus, and the aetiological agent of anthrax, Bacillus anthracis [15][16][17][18] . We have 10 years of experience developing this model for this use.…”

Section: History Of the Development Of Lung Tissue Modelsmentioning

confidence: 99%

“…A slice thickness of 500 to 700 m has been reported to be the optimal thickness for lung slices and has been used by other investigators. 23,24 For most of our studies, including those to measure cytokine induction or the purification of protein or RNA, we create 500 to 700 m thick slices [16][17][18]22 . We recently have begun cutting 200 to 300 m thick slices, which are being used in studies employing confocal fluorescence microscopy and subsequent computer-generated three-dimensional reconstruction of the lung architecture to study cell-specific host/pathogen interactions within whole tissue slices 26,27 .…”

Section: Inflation and Slicingmentioning

confidence: 99%