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...
The McMurdo Dry Valleys in Antarctica are a cold hyperarid polar desert that present extreme challenges to life. Here, we report a culture-independent survey of multidomain microbial biodiversity in McKelvey Valley, a pristine example of the coldest desert on Earth. We demonstrate that life has adapted to form highly-specialized communities in distinct lithic niches occurring concomitantly within this terrain. Endoliths and chasmoliths in sandstone displayed greatest diversity, whereas soil was relatively depauperate and lacked a significant photoautotrophic component, apart from isolated islands of hypolithic cyanobacterial colonization on quartz rocks in soil contact. Communities supported previously unreported polar bacteria and fungi, but archaea were absent from all niches. Lithic community structure did not vary significantly on a landscape scale and stochastic moisture input due to snowmelt resulted in increases in colonization frequency without significantly affecting diversity. The findings show that biodiversity near the cold-arid limit for life is more complex than previously appreciated, but communities lack variability probably due to the high selective pressures of this extreme environment.
Background: Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells.
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