Chemokine up-regulation in SARS-coronavirus–infected, monocyte-derived human dendritic cells

Abstract

Lymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was ob- IntroductionCoronaviruses (CoVs) comprise a large family of RNA viruses that infect a broad range of vertebrates, from mammalian to avian species. 1 Prior to the emergence of severe acute respiratory syndrome (SARS) in 2002 to 2003, human CoVs were known to be associated mainly with relatively mild upper respiratory diseases such as the common cold. The novel SARS-CoV, however, caused severe, rapidly progressive atypical pneumonia with fever, myalgia, and diarrhea. 2,3 The detection of virus in stool and urine in addition to the respiratory tract of patients with SARS further suggested that SARS is a systemic disease. 4,5 At autopsy, white pulp atrophy was observed in the spleen, and there was lymphoid depletion in lymph nodes. [6][7][8] Together with lymphopenia and increasing viral load in the first 10 days of disease, 3,4,6 these clinical features strongly suggest an evasion of the immune system by SARS-CoV. As with other viral infections, such as measles, this lymphoid depletion may have pathogenic significance.Dendritic cells (DCs) are antigen-presenting cells that play key roles in linking innate and adaptive immunity. 9-11 Immature DCs reside in the respiratory tract for immune surveillance, and they respond dynamically to local tissue inflammation in the airways and the distal lung. 12,13 They express a wide range of receptors, including c-type lectins 14,15 and toll-like receptors, 16,17 for the recognition of conserved pathogen patterns. Dendritic cells signal the presence of danger to cells of the adaptive immune response and modulate their responses via the secretion of proinflammatory and/or antiviral cytokines. 18 In particular, DCs secrete cytokines to polarize T-helper (Th) cells toward the Th1 or Th2 subsets. 10 The migration of DCs from tissues to lymph nodes is essential for antigen presentation and triggering of adaptive immune responses. The trafficking of DCs is regulated by chemokines that can be classified as homeostatic (constitutively expressed) or inflammatory (induced/augmented) according to their immune fuctions. [19][20][21] Acute respiratory viruses commonly induce inflammatory chemokines, such as macrophage inflammatory protein 1␣ (MIP-1␣), regulated upon activation, normal T cell expressed and secreted (RANTES), interferon-inducible protein of 10 kDa (IP-10), and monocyte chemotactic protein 1 (MCP-1), in local tissues. 21 Dendritic cells are also a major source of these chemokines. 20 On the basis of the function of DCs in immune surveillance, priming, a...

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

“…Moreover, the strong atrophic process of the thymus observed during HPAIV infection is a common feature of severe diseases like AIDS, rabies, and Chagas disease (19). Our results give rise to the assumption that this mechanism of increased pathogenesis is not only due to influenza viruses with pandemic potential, but also to infections with other new or re-emerging pathogens like foot-and-mouth disease virus, Chikungunya, severe acute respiratory syndrome, and West Nile Virus (20)(21)(22)(23)(24).…”

Lipopolysaccharide Induces IL-6 Production in Respiratory Syncytial Virus-Infected Airway Epithelial Cells Through the Toll-Like Receptor 4 Signaling Pathway

“…Endotoxin, or its purified derivative LPS, a cell wall component of Gramnegative bacteria, is a potent proinflammatory constituent continuously shedding into the environment, which is important in the pathogenesis of airway inflammatory diseases such as asthma. To study whether LPS-induced cytokine or chemokine production in noninfected airway epithelial cells, we chose chemokine CXC family member IL-8, IL-6 cytokine and the chemokine CCL family member RANTES as examples, as they also play a pivotal role in airway immune response to RSV infection (15,19). We found that incubation with 50 g/mL LPS (the dose choosing data were not shown) slightly up-regulated IL-6 production in 9HTEo cells (Fig.…”

“…First, standard PCR was performed in a total volume of 25 L and PCR conditions were 63°C for 60 s for 39 cycles. Second, synthesized cDNA was diluted (1:10) and quantified by real-time PCR using the Taqman Technology (Applied Biosystems, CA) as described previously (15). The ␤-actin gene was amplified as an internal control.…”

“…Cells (ϳ2.5 ϫ 10 5 ) were harvested at 3, 6, and 9 h post RSV infection and total RNA was extracted by TRIzol Reagent (Invitrogen Life Technologies, USA). Reverse transcription was performed as previously described (15). First, standard PCR was performed in a total volume of 25 L and PCR conditions were 63°C for 60 s for 39 cycles.…”

Influenza Virus Directly Infects Human Natural Killer Cells and Induces Cell Apoptosis

“…NK cells were exposed to influenza virus on ice for 90 min to allow viral binding and then shifted to 37°C for viral internalization. Twenty minutes later, cells were washed and fixed in 2.5% glutaraldehyde, followed by processing for electron microscopy as described in our previous study (19). The ultrathin section was viewed on a Philips EM208S transmission electron microscope (Philips Electron Optics).…”