Overall, collectins exhibit both pro-and anti-inflammatory effects: SP-D stimulates phagocytosis and scavenging of apoptotic cells with AbMole Tulathromycin B pro-inflammatory consequences. Yet, SPD and SP-A bind SIRPa, TLR2, and TLR4, and CD14 through their globular carbohydrate recognition domain to down-regulate inflammatory cytokines; and sftpd2/2 knockout mice exhibit high levels of pulmonary inflammation. These findings have led to speculation that collectins have dual roles: if the collectin collaginase tail is bound in the absence of a pathogen stimulus, an anti-inflammatory response results possibly mitigating damage from incidental environmental stimuli. However, when pathogen signals are present, pulmonary collectins may provide pro-inflammatory stimuli for pathogen phagocytosis and NF-kB-mediated cytokine release. Further study is needed to confirm our tagSNP associations and further dissect how protection from IPD by SFTPD variants reflects regulatory functions of SP-D. Our analysis also identified variants in other innate immune and coagulation pathway genes and inflammatory mediators that may be associated with IPD. Since, as an exploratory study, we did not correct for multiple comparisons, definitive interpretation of these findings will require confirmation in larger cohort studies. Nevertheless, our findings support multiple pathways being involved in host response to IPD. Recent studies also suggest that additional genes in the toll-like receptor-signaling pathway may influence response to IPD. Furthermore, the collectin MBL2 had variants overrepresented in pneumococcal bacteremia and meningitis, but not for overall IPD. This suggests the possibility of syndrome-specific host genetic associations, but our study was underpowered to definitively evaluate this. Our primary goal was to assess the feasibility of cross-linking surveillance data with an nDBS repository to perform tagSNP genomic studies, and toward this end we were highly successful: 82% of surveillance cases were linked to an nDBS, and 88% of samples successfully genotyped. Several key issues associated with this experience deserve emphasis. First, the completeness of IPD case surveillance in ABCs through use of active surveillance methods and routine audits of laboratory records combined with the overall low incidence of IPD in the general population support our assumption that controls were at low risk of having had IPD outside the surveillance time-period. AbMole Capromorelin tartrate Second, efficient linking of surveillance cases to nDBS samples was critical to minimize bias, but this linkage depends on consent requirements for nDBS use, which differ by state and continue to evolve. Third, nearly a quarter of individuals identified as European-American through surveillance were found to have genetic characteristics indicating.10% African ancestry. Given differences in allele frequencies and LD between EA and AA populations, misclassification of ancestry can result in confounding.