Mannose-Binding Lectin in Severe Acute Respiratory Syndrome Coronavirus Infection

Abstract

Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an anteantibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose-and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARSCoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS.Severe acute respiratory syndrome (SARS), a newly emerged infectious disease of humans, has affected 125 countries, with 8098 cases and 774 deaths reported to the World Health Organization (WHO) during the first half of 2003 [1]. The most affected locations were mainland China, Hong Kong, Taiwan, Singapore, and To-

Mannose-Binding Lectin (MBL) Facilitates Opsonophagocytosis of Yeasts but Not of Bacteria despite MBL Binding

“…In vitro addition of exogenous MBL (5-fold excess) increased C3 deposition on yeasts as well as their uptake by phagocytes. Our results are in agreement with the binding of MBL to C. albicans described previously (32,33), also reporting a MBL-dependent enhancement of C3 deposition and decrease of disseminating candidiasis in mice upon MBL administration. MBL replacement therapy as appropriate (adjuvant) treatment has been suggested for patients with MBL deficiency and disseminated candidiasis.…”

Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms

“…31 Individuals homozygous for the p.D120G mutation have no MBL pathway activity. 20 Except for this situation we surprisingly find no correlation between MASP-2 concentrations and MBL pathway activity.…”

Mannose-Binding Lectin Deficiency and Respiratory Tract Infection

“…[4] Chlamydia pneumoniae and Chlamydia psittaci are bound by MBL with inhibition of their growth in cell culture, albeit at much higher inhibitory concentrations than for Chlamydia trachomatis [25] . Pseudomonas aeruginosa , an important pathogen in cystic fibrosis (CF), was initially not thought to be bound by MBL in studies using flow cytometry [19] .…”

“…Two case control studies of Chinese patients showed an association between carriage of the B variant MBL2 allele, the only MBL2 structural variant found in the Chinese population, and predisposition to SARS [4,50] . There was no association between low MBL2 haplotypes and death due to SARS.…”