Lower mannose-binding lectin contributes to deleterious H1N1 2009 infection in children

Gao, Lailong; Shang, Shuai; Zhang, ChenMei; Tong, Meiqin; Chen, Yinghu

doi:10.1111/apm.12111

Cited by 7 publications

(10 citation statements)

References 10 publications

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“…However, other studies in adults have not found MBL to be associated with risk for sepsis (39–42) or have reported a more nuanced picture that includes a mixture of both pro-inflammatory and anti-infection effects which may be beneficial or detrimental in varying disease states. (33, 34, 43) Specifically in pediatrics, six studies have demonstrated an association between lower MBL levels, or low-MBL producing haplotypes, and increased severity of infection-related disease (4, 5, 15, 16, 44–46) while five studies showed similar findings to ours with a lack of association (12, 46–50) and two studies concluded a possible protective role for low-producing MBL genotypes or levels. (12, 51)…”

Section: Discussionsupporting

confidence: 69%

“…(4, 11, 12, 16, 19, 33–38) We did find that MBL levels were diluted in patients that received extremely high volumes of fluid in the first 24 hours; a common occurrence in patients with severe sepsis that could possibly confound the relationship between MBL levels and infection-related critical illness. MBL levels were strongly genetically influenced by the combination of high, intermediate and low producing haplotypes.…”

Section: Discussionmentioning

confidence: 84%

“…(6, 10, 12–14) It is unclear if there is an advantage to low-producing haplotypes although some have speculated MBL may worsen clinical presentation of infections that cause damage mainly by inflammatory responses. (6, 10, 14–16) Previous studies assessing the relationship between MBL levels and critical illness have varied in cohort size, the population studied, the outcome assessed, and whether/how MBL genotype was evaluated. We speculate that this may have led to the conflicting reports on whether MBL is associated with severe infection.…”

Section: Introductionmentioning

confidence: 99%

“…We speculate that this may have led to the conflicting reports on whether MBL is associated with severe infection. (7, 16–21) In addition, potentially confounding variables such as fluid administration could dilute MBL levels and influence the association.…”

Section: Introductionmentioning

confidence: 99%

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Mannose-Binding Lectin Levels in Critically Ill Children With Severe Infections*

Madsen

Levy

Madden

et al. 2017

Pediatric Critical Care Medicine

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Objective Low mannose-binding lectin (MBL) levels and haplotypes associated with low MBL production have been associated with infection and severe sepsis. We tested the hypothesis that MBL levels would be associated with severe infection in a large cohort of critically ill children. Design Prospective cohort study Setting Medical and Surgical Pediatric Intensive Care Units (PICUs), Boston Children’s Hospital Patients Children < 21 years of age admitted to the intensive care units from November 2009 to November 2010. Interventions None Measurements and Main Results We measured MBL levels in 479/520 (92%) consecutively admitted children with severe or life-threatening illness. We genotyped 213 Caucasian children for MBL haplotype tagging variants and assigned haplotypes. In the univariate analyses of MBL levels with pre-admission characteristics, levels were higher in patients with pre-existing renal disease. Patients who received >100 ml/kg of fluids in the first 24 hours after admission had markedly lower MBL, as did patients post-spinal fusion surgery. MBL levels had no association with infection status on admission, or with progression from systemic inflammatory response syndrome to sepsis or septic shock. Although MBL haplotypes strongly influenced MBL levels in the predicted relationship, low MBL-producing haplotypes were not associated with increased risk of infection. Conclusions Mannose-binding lectin levels are largely genetically determined. This relationship was preserved in children during critical illness, despite the effect of large-volume fluid administration on MBL levels. Previous literature evaluating an association between MBL levels and severe infection is inconsistent; we found no relationship in our PICU cohort. We found that MBL levels were lower after aggressive fluid resuscitation, and suggest that studies of MBL in critically ill patients should assess MBL haplotypes to reflect pre-illness levels.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mannose-Binding Lectin Levels in Critically Ill Children With Severe Infections*

Madsen

Levy

Madden

et al. 2017

Pediatric Critical Care Medicine

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“…Serum levels of MBL in children were shown to be significantly higher than that in adults (4 ± 3.960 μg/mL and 2.207 ± 1.73 μg/mL, respectively) . The mean serum level of MBL in children is higher than the MIC 50 required to inhibit influenza A(H1N1)pdm09, while in adults, it is lower than the MIC50, which may explain the protective effect of MBL in children . There are very few reports about the effect of high doses of MBL on influenza A(H1N1)pdm09 infection in humans.…”

mentioning

confidence: 99%

High doses of recombinant mannan‐binding lectin inhibit the binding of influenza A(H1N1)pdm09 virus with cells expressing DC‐SIGN

Shang

Tao

et al. 2017

APMIS

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The pandemic influenza A (H1N1)pdm09 virus continues to be a threat to human health. Low doses of mannan-binding lectin (MBL) (<1 μg/mL) were shown not to protect against influenza A(H1N1)pdm09 infection. However, the effect of high doses of MBL has not been investigated. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) has been proposed as an alternative receptor for influenza A(H1N1)pdm09 virus. In this study, we examined the expression of DC-SIGN on DCs as well as on acute monocytic leukemia cell line, THP-1. High doses of recombinant or human MBL inhibited binding of influenza A(H1N1)pdm09 to both these cell types in the presence of complement derived from bovine serum. Further, anti-DC-SIGN monoclonal antibody inhibited binding of influenza A(H1N1)pdm09 to both DC-SIGN-expressing DCs and THP-1 cells. This study demonstrates that high doses of MBL can inhibit binding of influenza A(H1N1)pdm09 virus to DC-SIGN-expressing cells in the presence of complement. Our results suggest that DC-SIGN may be an alternative receptor for influenza A(H1N1)pdm09 virus.

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Influenza virus N-linked glycosylation and innate immunity

2019

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Influenza viruses cause seasonal epidemics and sporadic pandemics in humans. The virus’s ability to change its antigenic nature through mutation and recombination, and the difficulty in developing highly effective universal vaccines against it, make it a serious global public health challenge. Influenza virus’s surface glycoproteins, hemagglutinin and neuraminidase, are all modified by the host cell’s N-linked glycosylation pathways. Host innate immune responses are the first line of defense against infection, and glycosylation of these major antigens plays an important role in the generation of host innate responses toward the virus. Here, we review the principal findings in the analytical techniques used to study influenza N-linked glycosylation, the evolutionary dynamics of N-linked glycosylation in seasonal versus pandemic and zoonotic strains, its role in host innate immune responses, and the prospects for lectin-based therapies. As the efficiency of innate immune responses is a critical determinant of disease severity and adaptive immunity, the study of influenza glycobiology is of clinical as well as research interest.

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Lower mannose-binding lectin contributes to deleterious H1N1 2009 infection in children

Cited by 7 publications

References 10 publications

Mannose-Binding Lectin Levels in Critically Ill Children With Severe Infections*

Mannose-Binding Lectin Levels in Critically Ill Children With Severe Infections*

High doses of recombinant mannan‐binding lectin inhibit the binding of influenza A(H1N1)pdm09 virus with cells expressing DC‐SIGN

Influenza virus N-linked glycosylation and innate immunity

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