In sharp contrast to the potentially proinflammatory effects after PAMP recognition by collectins, mice deficient in SP-A or SP-D develop enhanced inflammatory pulmonary responses [35] [36] [37] . SP-A and SP-D play a dual role in the inflammatory response. They interact with pathogens via their CRD, and are recognized by calreticulin/CD91 on phagocytes through the N-terminal collagen domain, promoting phagocytosis and proinflammatory responses [10, 13] . By contrast, binding of the CRD to signal inhibitory regulatory protein α (SIRPα) on alveolar macrophages suppresses NF-B activation and inflammation, allowing the lung to remain in a quiescent state during periods of health [10] . A similar dual effect is observed in the promotion or inhibition of apoptosis [12] . SP-A and SP-D can also inhibit inflammation by blocking, through the CRD, Toll-like receptors 2 and 4 [38, 39] . In agreement with previous results [16] , we have observed that the SFTPD aa11-C allele associates with significantly lower SP-D serum levels than the aa11-T allele, and this effect was dose-dependent. The aa11-C/T SNP, located in the Nterminal domain, influences oligomerization of SP-D and explains a significant part of the heritability of serum SP-D levels [16, 40] . Serum from aa11-C homozygotes lack the highest molecular weight (m.w.) forms of the protein, which binds preferentially to complex microorganisms whereas the low m.w. SP-D preferentially binds LPS [16] .