Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages

Surfactant protein-D (SP-D) is a collectin produced in the distal lung airs paces that is believed to play an important role in innate pulmonary immuni ty. Naive immunologic responses to Mycobacterium tuberculosis (M.tb) are es pecially important in the lung, since entry of this inhaled pathogen into t he alveolar macrophage is a pivotal event in disease pathogenesis, Here we investigated SP-D binding to M,tb and the effect of this binding on the adh erence of M,tb to human macrophages. These studies demonstrate specific bin ding of SP-D to M,tb that is saturable, calcium dependent, and carbohydrate inhibitable, In addition to purified SP-D, SP-D in bronchoalveolar lavage fluids from healthy donors and patients with alveolar proteinosis also bind s to M.tb. Incubation of M,tb with SP-D results in agglutination of the bac teria. In contrast to its binding to M.tb, SP-D binds minimally to the avir ulent Mycobacterium smegmatis. SP-D binds predominantly to lipoarabinomanna n from the virulent Erdman strain of M.tb, but not the lipoarabinomannan fr om M, smegmatis. The binding of SP-D to Erdman lipoarabinomannan Is mediate d by the terminal mannosyl oligosaccharides of this lipoglycan, Incubation of M.tb with subagglutinating concentrations of SP-D leads to reduced adher ence of the bacteria to macrophages (62.7% of control adherence +/- 3.2% SE M, n = 8), whereas incubation of bacteria with surfactant protein A leads t o significantly increased adherence to monocyte-derived macrophages. These data provide evidence for specific binding of SP-D to M, tuberculosis and i ndicate that SP-D and surfactant protein A serve different roles in the inn ate host response to this pathogen in the lung.