Mannose-binding lectin is present in the infected airway: a possible pulmonary defence mechanism

Fidler, Katy; Hilliard, Tom; Bush, Andy; Johnson, Marina; Geddes, Duncan M.; Turner, Malcolm; Alton, Eric W.F.W.; Klein, Nigel; Davies, Jane C.

doi:10.1136/thx.2008.100073

Cited by 60 publications

(56 citation statements)

References 42 publications

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“…The literature shows MBL to consistently have an important central role in lung defences via complement activation, apoptosis and phagocytosis with cytokine modulation via the macrophage mannose receptor (MMR) [17]. Studies show that low MBL levels impair MMR function reducing the innate immune response.…”

Section: Discussionmentioning

confidence: 99%

“…It is part of the innate immune response and also functions as an acute phase protein [15,16], with elevation in levels by 1.5-3 fold in systemic inflammation associated with elevation of c-reactive protein. It is a member of the collectin family and as a C-lectin is in the same family as surfactant proteins A and D. MBL works as a PAMP (Pathogen Associated Molecular Patterns), recognising repeating sugars on the surface of bacteria, fungi, viruses & parasites resulting in its immune system activation [17].…”

Section: Introductionmentioning

confidence: 99%

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The Deficiency of Serum Mannose Binding Lectin in Early Onset Idiopathic Pulmonary Fibrosis and Familial Cases

VA¹

2012

J Clin Cell Immunol

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Deficiency of Serum Mannose Binding Lectin in Early Onset Idiopathic Pulmonary Fibrosis and Familial Cases

VA¹

2012

J Clin Cell Immunol

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“…MBL is generally considered to be a plasma protein, produced in the liver as an acute-phase reactant, and secreted into the circulation, yet MBL has been detected in human BAL (18,28) and in BAL from influenza virusinfected mice (15), suggesting it can transude into the airways during inflammation of the lung. As airway epithelial cells represent the primary target of influenza virus infection in the human respiratory tract, SP-D and MBL may represent an important barrier to establishment of infection of epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…In humans, members of the collectin family that mediate antiviral activity against influenza viruses in vitro include surfactant protein (SP)-D, SP-A, and MBL. SP-D and MBL bind to mannose-rich glycans on the hemagglutinin (HA) and neuraminidase (NA) glycoproteins of different virus strains to inhibit the hemagglutinating activity of the virus (13)(14)(15), neutralize virus infectivity (14-16), aggregate virions (14,(16)(17)(18), and inhibit the enzymatic activity of the viral NA (19,20). SP-D is particularly potent in its ability to inhibit virus strains bearing high levels of glycosylation on the globular head of HA (14,15,21,22).…”

Section: S Ince April 2009 a Global Outbreak Caused By The Novel Panmentioning

confidence: 99%

Pandemic H1N1 Influenza A Viruses Are Resistant to the Antiviral Activities of Innate Immune Proteins of the Collectin and Pentraxin Superfamilies

Job

Deng

Tate

et al. 2010

The Journal of Immunology

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Acquired immune responses elicited to recent strains of seasonal H1N1 influenza viruses provide limited protection against emerging A(H1N1) pandemic viruses. Accordingly, pre-existing or rapidly induced innate immune defenses are of critical importance in limiting early infection. Respiratory secretions contain proteins of the innate immune system, including members of the collectin and pentraxin superfamilies. These mediate potent antiviral activity and act as an initial barrier to influenza infection. In this study, we have examined the sensitivity of H1N1 viruses, including pandemic virus strains, for their sensitivity to collectins (surfactant protein [SP]-D and mannose-binding lectin [MBL]) and to the pentraxin PTX3. Human SP-D and MBL inhibited virus-induced hemagglutinating activity, blocked the enzymatic activity of the viral neuraminidase, and neutralized the ability of H1N1 viruses to infect human respiratory epithelial cells in a manner that correlated with the degree of glycosylation in the globular head of the hemagglutinin. Recent seasonal H1N1 viruses expressed three to four N-glycosylation sequons on the head of hemagglutinin and were very sensitive to inhibition by SP-D or MBL, whereas A(H1N1) pandemic viruses expressed a single N-glycosylation sequon and were resistant to either collectin. Of interest, both seasonal and pandemic H1N1 viruses were resistant to PTX3. Thus, unlike recent seasonal H1N1 strains of influenza virus, A(H1N1) pandemic viruses are resistant to the antiviral activities of innate immune proteins of the collectin superfamily.

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“…12,13). Surfactant protein-D (SP-D) and mannose-binding lectin (MBL) inhibit IAV-induced hemagglutination activity (14,15), as well as mediating virus aggregation (14,16,17) and neutralization of virus infectivity (14)(15)(16). SP-D is constitutively expressed within the airways, whereas MBL is produced by the liver but can translocate into the airways during IAV infection (15).…”

mentioning

confidence: 99%

Addition of Glycosylation to Influenza A Virus Hemagglutinin Modulates Antibody-Mediated Recognition of H1N1 2009 Pandemic Viruses

Job

Deng

Barfod

et al. 2013

The Journal of Immunology

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Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the viral hemagglutinin (HA). Glycans on the head of HA promote virus survival by shielding antigenic sites, but highly glycosylated seasonal IAV are inactivated by soluble lectins of the innate immune system. In 2009, human strains of pandemic H1N1 [A(H1N1)pdm] expressed a single glycosylation site (Asn104) on the head of HA. Since then, variants with additional glycosylation sites have been detected, and the location of these sites has been distinct to those of recent seasonal H1N1 strains. We have compared wild-type and reverse-engineered A(H1N1)pdm IAV with differing potential glycosylation sites on HA for sensitivity to collectins and to neutralizing Abs. Addition of a glycan (Asn136) to A(H1N1)pdm HA was associated with resistance to neutralizing Abs but did not increase sensitivity to collectins. Moreover, variants expressing Asn136 showed enhanced growth in A(H1N1)pdm-vaccinated mice, consistent with evasion of Ab-mediated immunity in vivo. Thus, a fine balance exists regarding the optimal pattern of HA glycosylation to facilitate evasion of Ab-mediated immunity while maintaining resistance to lectin-mediated defenses of the innate immune system.

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Mannose-binding lectin is present in the infected airway: a possible pulmonary defence mechanism

Abstract: ABSTRACT

Cited by 60 publications

References 42 publications

The Deficiency of Serum Mannose Binding Lectin in Early Onset Idiopathic Pulmonary Fibrosis and Familial Cases

The Deficiency of Serum Mannose Binding Lectin in Early Onset Idiopathic Pulmonary Fibrosis and Familial Cases

Pandemic H1N1 Influenza A Viruses Are Resistant to the Antiviral Activities of Innate Immune Proteins of the Collectin and Pentraxin Superfamilies

Addition of Glycosylation to Influenza A Virus Hemagglutinin Modulates Antibody-Mediated Recognition of H1N1 2009 Pandemic Viruses

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