The SARS coronavirus spike glycoprotein is selectively recognized by lung surfactant protein D and activates macrophages

Leth-Larsen, Rikke; Zhong, Fei; Chow, Vincent T. K.; Holmskov, Uffe; Lu, Jinhua

doi:10.1016/j.imbio.2006.12.001

Cited by 110 publications

(121 citation statements)

References 47 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…The slight decrease in SP-D could enhance the SARS infection, although this is unlikely, based on our experiments with 229E-6V (another coronavirus), in which SP-D did not make a major difference in the 229E-6V infectability of human alveolar macrophages (45). Nevertheless, SP-D has been reported to interact with the SARS spike glycoprotein, the attachment protein (46).…”

Section: Discussionmentioning

confidence: 82%

Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus

Qian

Travanty

Oko

et al. 2013

Am J Respir Cell Mol Biol

286

266

View full text Add to dashboard Cite

Severe acute respiratory syndrome (SARS)-coronavirus (CoV) produces a devastating primary viral pneumonia with diffuse alveolar damage and a marked increase in circulating cytokines. One of the major cell types to be infected is the alveolar type II cell. However, the innate immune response of primary human alveolar epithelial cells infected with SARS-CoV has not been defined. Our objectives included developing a culture system permissive for SARS-CoV infection in primary human type II cells and defining their innate immune response. Culturing primary human alveolar type II cells at an airliquid interface (A/L) improved their differentiation and greatly increased their susceptibility to infection, allowing us to define their primary interferon and chemokine responses. Viral antigens were detected in the cytoplasm of infected type II cells, electron micrographs demonstrated secretory vesicles filled with virions, virus RNA concentrations increased with time, and infectious virions were released by exocytosis from the apical surface of polarized type II cells. A marked increase was evident in the mRNA concentrations of interferon-b and interferon-l (IL-29) and in a large number of proinflammatory cytokines and chemokines. A surprising finding involved the variability of expression of angiotensin-converting enzyme-2, the SARS-CoV receptor, in type II cells from different donors. In conclusion, the cultivation of alveolar type II cells at an air-liquid interface provides primary cultures in which to study the pulmonary innate immune responses to infection with SARS-CoV, and to explore possible therapeutic approaches to modulating these innate immune responses.Keywords: lung innate immune response; cytokine responses to SARS coronavirus; lung cell differentiation; air-liquid interface culturesSevere acute respiratory syndrome-associated coronavirus (SARSCoV) produces devastating viral pneumonia (1, 2). Pathologic changes are most prominent in the lungs, with disruptions of the epithelium in gas exchange areas and conducting airways (2-4). The epithelial cells of the alveoli and the conducting airways are the primary targets of SARS-CoV in the human lung, and they express the SARS receptor, angiotension-converting enzyme-2 (ACE2) (5-8). In autopsies of patients with SARS, coronavirus RNA and proteins have been detected in type II cells via immunocytochemisty and in situ hybridization (7,(9)(10)(11)(12)(13)(14). In the aged macaque model of SARS, in which the initial site of infection in the lung can be studied, virus infection was detected in both alveolar type I and type II cells (11,15). In human SARS autopsy specimens, the infection of alveolar macrophages was also suggested because they contained SARS antigens and formed multinucleated giant cells (2, 11). However, in vitro human alveolar macrophages, monocyte-derived dendritic cells, and monocytes are not readily susceptible to SARS-CoV, and these cell types show only very modest cytokine and interferon responses upon exposure to SARS-CoV (16-21).One of the major...

show abstract

Section: Discussionmentioning

confidence: 82%

Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus

Qian

Travanty

Oko

et al. 2013

Am J Respir Cell Mol Biol

286

266

View full text Add to dashboard Cite

show abstract

“…Thus, SP-A, SP-B, and SP-D are generated by alveolar type II and airway epithelial cells, while SP-C is exclusively synthesized by type II cells. Also known as collectins, SP-A and SP-D facilitate the elimination of invading pathogens by enhancing phagocytic activity of macrophages (23,38,39). SP-A-deficient mice exhibit an exaggerated inflammatory response to influenza virus infection (40).…”

Section: Discussionmentioning

confidence: 99%

“…The alveolar lining is covered by alveolar type I and type II epithelial cells, which play essential roles in fluid balance and in secretion of surfactant proteins SP-A, SP-B, SP-C, and SP-D (21)(22)(23)(24). Although enhanced lethality in macrophage-depleted animals is attributed to elevated virus titers, the fate of alveolar epithelial cells in macrophage-depleted animals after influenza virus infection is unclear.…”

mentioning

confidence: 99%

MCP-1 Antibody Treatment Enhances Damage and Impedes Repair of the Alveolar Epithelium in Influenza Pneumonitis

Narasaraju¹,

Ng²,

Phoon³

et al. 2010

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Recent studies have demonstrated an essential role of alveolar macrophages during influenza virus infection. Enhanced mortalities were observed in macrophage-depleted mice and pigs after influenza virus infection, but the basis for the enhanced pathogenesis is unclear. This study revealed that blocking macrophage recruitment into the lungs in a mouse model of influenza pneumonitis resulted in enhanced alveolar epithelial damage and apoptosis, as evaluated by histopathology, immunohistochemistry, Western blot, RT-PCR, and TUNEL assays. Abrogation of macrophage recruitment was achieved by treatment with monoclonal antibody against monocyte chemoattractant protein-1 (MCP-1) after sub-lethal challenge with mouse-adapted human influenza A/Aichi/2/68 virus. Interestingly, elevated levels of hepatocyte growth factor (HGF), a mitogen for alveolar epithelium, were detected in bronchoalveolar lavage samples and in lung homogenates of control untreated and nonimmune immunoglobulin (Ig)G-treated mice after infection compared with anti-MCP-1-treated infected mice. The lungs of control animals also displayed strongly positive HGF staining in alveolar macrophages as well as alveolar epithelial cell hyperplasia. Co-culture of influenza virus-infected alveolar epithelial cells with freshly isolated alveolar macrophages induced HGF production and phagocytic activity of macrophages. Recombinant HGF added to mouse lung explants after influenza virus infection resulted in enhanced BrdU labeling of alveolar type II epithelial cells, indicating their proliferation, in contrast with anti-HGF treatment showing significantly reduced epithelial regeneration. Our data indicate that inhibition of macrophage recruitment augmented alveolar epithelial damage and apoptosis during influenza pneumonitis, and that HGF produced by macrophages in response to influenza participates in the resolution of alveolar epithelium.

show abstract

“…Two important proteins of the innate immune system in the gas exchange portion of the lung are surfactant proteins A and D (Haagsman et al, 2008;Pastva et al, 2007), both of which have been reported to be important in controlling viral infections (Doss et al, 2009;Leth-Larsen et al, 2007). BALF samples from SDAV and control rats were assayed for surfactant proteins SP-A and SP-D using ELISA (Fig.…”

Section: Rat Lung Infection By Sdav Induces Expression Of Cytokines Lmentioning

confidence: 99%

Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response

Funk

Manzer

Miura

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

The rat coronavirus sialodacryoadenitis virus (SDAV) causes respiratory infection and provides a system for investigating respiratory coronaviruses in a natural host. A viral suspension in the form of a microspray aerosol was delivered by intratracheal instillation into the distal lung of 6-8-weekold Fischer 344 rats. SDAV inoculation produced a 7 % body weight loss over a 5 day period that was followed by recovery over the next 7 days. SDAV caused focal lesions in the lung, which were most severe on day 4 post-inoculation (p.i.). Immunofluorescent staining showed that four cell types supported SDAV virus replication in the lower respiratory tract, namely Clara cells, ciliated cells in the bronchial airway and alveolar type I and type II cells in the lung parenchyma. In bronchial alveolar lavage fluid (BALF) a neutrophil influx increased the population of neutrophils to 45 % compared with 6 % of the cells in control samples on day 2 after mock inoculation. Virus infection induced an increase in surfactant protein SP-D levels in BALF of infected rats on days 4 and 8 p.i. that subsided by day 12. The concentrations of chemokines MCP-1, LIX and CINC-1 in BALF increased on day 4 p.i., but returned to control levels by day 8. Intratracheal instillation of rats with SDAV coronavirus caused an acute, self-limited infection that is a useful model for studying the early events of the innate immune response to respiratory coronavirus infections in lungs of the natural virus host. INTRODUCTIONThe large volume of air inhaled each day and the extensive surface area of the lung makes the respiratory system especially vulnerable to airborne infectious agents. These pathogens include many respiratory viruses such as influenza virus, respiratory syncytial virus, rhinovirus and coronaviruses (CoVs). Respiratory tract infections are the leading cause of infectious disease globally (WHO, 2004). The outbreak of severe acute respiratory syndrome (SARS) in [2002][2003] emphasized the vulnerability of humans to respiratory virus diseases and the potential for high morbidity and mortality in viral infections of the lower respiratory tract. The aetiological agent of SARS was identified as a coronavirus (SARS-CoV) derived from an animal reservoir (Fouchier et al., 2003). Besides human infections, CoVs cause respiratory, enteric and neurological infections in a variety of birds and mammals (Weiss & Navas-Martin, 2005). Five human CoVs have been identified to date, all of which cause respiratory tract infections. Human CoVs 229E and OC43 were first identified in the 1960s, and they cause up to 15-35 % of the adult colds in otherwise healthy individuals (Kahn & McIntosh, 2005). After the discovery of SARS-CoV, two additional human CoVs were identified, NL63 and HKU1 (van der Hoek et al., 2004;Woo et al., 2005). On a global basis, the human CoVs 229E, OC43, HKU1 and NL63 are estimated to cause approximately 10 % of all hospitalizations of children for respiratory tract infections (Gerna et al., 2007;Vabret et al., 2008).A number of animal mod...

show abstract

The SARS coronavirus spike glycoprotein is selectively recognized by lung surfactant protein D and activates macrophages

Cited by 110 publications

References 47 publications

Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus

Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus

MCP-1 Antibody Treatment Enhances Damage and Impedes Repair of the Alveolar Epithelium in Influenza Pneumonitis

Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response

Contact Info

Product

Resources

About