The Distinctive Features of Influenza Virus Infection of Dendritic Cells

Bender, Armin; Albert, Matthew L.; Reddy, Anita; Feldman, M; Sauter, Birthe; Kaplan, Gilla; Hellman, Wilhelmine; Bhardwaj, Nina

doi:10.1016/s0171-2985(98)80078-8

Cited by 101 publications

(83 citation statements)

References 35 publications

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“…Given that levels of IFN-β and IRF-7 were similar in nontargeting cells ex vivo (Fig. 4B), these data suggest that IAV replication within hematopoietic cells, despite being a nonproductive site of infection (42), is critical for the induction of the host innate response to virus.…”

Section: Iav Amplification Within Hematopoietic Cells Is Critical Formentioning

confidence: 76%

Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses

Langlois¹,

Varble²,

Chua³

et al. 2012

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

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A coordinated innate and adaptive immune response, orchestrated by antigen presenting cells (APCs), is required for effective clearance of influenza A virus (IAV). Although IAV primarily infects epithelial cells of the upper respiratory tract, APCs are also susceptible. To determine if virus transcription in these cells is required to generate protective innate and adaptive immune responses, we engineered IAV to be selectively attenuated in cells of hematopoietic origin. Incorporation of hematopoietic-specific miR-142 target sites into the nucleoprotein of IAV effectively silenced virus transcription in APCs, but had no significant impact in lung epithelial cells. Here we demonstrate that inhibiting IAV replication in APCs in vivo did not alter clearance, or the generation of IAV-specific CD8 T cells, suggesting that cross-presentation is sufficient for cytotoxic T lymphocyte activation. In contrast, loss of in vivo virus infection, selectively in APCs, resulted in a significant reduction of retinoic acid-inducible gene I-dependent type I IFN (IFN-I). These data implicate the formation of virus replication intermediates in APCs as the predominant trigger of IFN-I in vivo. Taking these data together, this research describes a unique platform to study the host response to IAV and provides insights into the mechanism of antigen presentation and the induction of IFN-I.

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Section: Iav Amplification Within Hematopoietic Cells Is Critical Formentioning

confidence: 76%

Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses

Langlois¹,

Varble²,

Chua³

et al. 2012

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

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“…The inhibition of viral replication in DCs is a common feature of many viruses. For example, mature DCs block vaccinia (10), influenza (33), HIV (34), and vesicular stomatitis virus (17) replication. The main mechanism implicated in the abortion of infection in DCs is the induction of IFN-␣␤ (17,35,36).…”

Section: Discussionmentioning

confidence: 99%

Impairment of Thymus-Dependent Responses by Murine Dendritic Cells Infected with Foot-and-Mouth Disease Virus

Ostrowski

Vermeulen

Zábal

et al. 2005

The Journal of Immunology

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Foot-and-mouth disease virus (FMDV) is a cytopathic virus that experimentally infects mice, inducing a thymus-independent neutralizing Ab response that rapidly clears the virus. In contrast, vaccination with UV-inactivated virus induces a typical thymus-dependent (TD) response. In this study we show that dendritic cells (DCs) are susceptible to infection with FMDV in vitro, although viral replication is abortive. Infected DCs down-regulate the expression of MHC class II and CD40 molecules and up-regulate the expression of CD11b. In addition, infected DCs exhibit morphological and functional changes toward a macrophage-like phenotype. FMDV-infected DCs fail to stimulate T cell proliferation in vitro and to boost an Ab response in vivo. Moreover, infection of DCs in vitro induces the secretion of IFN-γ and the suppressive cytokine IL-10 in cocultures of DCs and splenocytes. High quantities of these cytokines are also detected in the spleens of FMDV-infected mice, but not in the spleens of vaccinated mice. The peak secretion of IFN-γ and IL-10 is concurrent with the suppression of Con A-mediated proliferation of T cells obtained from the spleens of infected mice. Furthermore, the secretion of these cytokines correlates with the suppression of the response to OVA, a typical TD Ag. Thus, infection of DCs with FMDV induces suppression of TD responses without affecting the induction of a protective thymus-independent response. Later, T cell responses are restored, setting the stage for the development of a long-lasting protective immunity.

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“…In vivo, murine DC containing internal Leishmania donovani (58) and L. major (59) also have been observed. Human DC have been reported to phagocytose Borrelia burgdorferi (36) and Mycobacterium tuberculosis (37), influenza (60), and measles (61) viruses and the protozoans Trypanosoma cruzi (39) and L. donovani (38).…”

Section: Discussionmentioning

confidence: 99%

Histoplasma capsulatumYeasts Are Phagocytosed Via Very Late Antigen-5, Killed, and Processed for Antigen Presentation by Human Dendritic Cells

Gildea

Morris

Newman

2001

The Journal of Immunology

104

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Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of world-wide importance. As the induction of cell-mediated immunity to Hc is of critical importance in host defense, we sought to determine whether dendritic cells (DC) could function as a primary APC for this pathogenic fungus. DC obtained by culture of human monocytes in the presence of GM-CSF and IL-4 phagocytosed Hc yeasts in a time-dependent manner. Upon ingestion, the intracellular growth of yeasts within DC was completely inhibited compared with rapid growth within human macrophages. Electron microscopy of DC with ingested Hc revealed that many of the yeasts were degraded as early as 2 h postingestion. In contrast to macrophages, human DC recognized Hc yeasts via the fibronectin receptor, very late Ag-5, and not via CD18 receptors. DC stimulated Hc-specific lymphocyte proliferation in a concentration-dependent manner after phagocytosis of viable and heat-killed Hc yeasts, but greater proliferation was achieved after ingestion of viable yeasts. These data demonstrate that human DC can phagocytose and degrade a fungal pathogen and subsequently process the appropriate Ags for stimulation of lymphocyte proliferation. In vivo, such interactions between DC and Hc may facilitate the induction of cell-mediated immunity.

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The Distinctive Features of Influenza Virus Infection of Dendritic Cells

Cited by 101 publications

References 35 publications

Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses

Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses

Impairment of Thymus-Dependent Responses by Murine Dendritic Cells Infected with Foot-and-Mouth Disease Virus

Histoplasma capsulatumYeasts Are Phagocytosed Via Very Late Antigen-5, Killed, and Processed for Antigen Presentation by Human Dendritic Cells

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