Murine models of Aspergillosis: Role of collectins in host defense.

Aspergillus fumigatus, a ubiquitous fungus, causes a wide spectrum of clinical conditions ranging from allergic to invasive aspergillosis depending upon the hosts’ immune status. Several animal models have been generated to mimic the human clinical conditions in allergic and invasive aspergillosis. The onset, duration and severity of the disease developed in models varied depending on the animal strain/fungal isolate, quantity and mode of administration of fungal antigens/spores, duration of the treatment, and type of immunosuppressive agent used. These models provide insight into host and pathogen factors and prove to be useful for evaluation of diagnostic markers and effective therapies. A series of studies established the protective role of collectins in murine models of Allergic Bronchopulmonary Aspergillosis and Invasive Pulmonary Aspergillosis. Collectins, namely surfactant protein A (SP-A), surfactant protein D (SP-D) and mannan binding lectin (MBL), are pattern recognition molecules regulating both innate and adaptive immune response against pathogens. In the present review, we discussed various murine models of allergic and invasive aspergillosis and the role of collectins in host defense against aspergillosis.

The potential of circulating endothelial progenitor cells to form colonies is inversely proportional to total vascular risk score in patients with coronary artery disease.

OBJECTIVE: The present study correlated the functional ability of culture-enriched EPCs to form colonies (EPC-CFUs), with risk factors and severity of CAD. METHODS: Blood mononuclear cells from healthy controls (n = 16) and patients with CAD (n =35) were cultured for seven days for the formation of EPC-CFUs. After the characterization of EPCs, the number of EPC-clusters were compared in the study groups and correlated with the presence or absence of individual CAD risk factors, total vascular risk score (TVRS) and the severity of CAD in patients with CAD by Student's 't' test and regression analysis. RESULTS: As compared to the patients, the controls showed significantly greater formation of EPC-CFUs. Patients with hypertension and smoking had significant reduction in the number of EPC-CFUs as compared to patients without these risk factors (p < 0.05). A negative correlation between TVRS and number of EPC-CFUs (r = -0.74, p < 0.05) and also between number of stenosing coronary arteries and EPC-CFUs (r = -0.42, p = 0.05) were observed. On multivariate analysis, however, only TVRS appeared to be a significant predictor of reduced formation of EPC-CFUs. CONCLUSION: The present study suggests that more is the number of CAD risk factors, lesser is the formation of EPC-clusters in culture.

Association of SP-D, MBL and I-NOS genetic variants with pulmonary tuberculosis.

Background: Pulmonary tuberculosis is caused by Mycobacterium tuberculosis . It is a multifactorial disease with both host as well as pathogen factors contributing to susceptibility and protection from the disease. Various reports have highlighted important roles of lung surfactant protein D (SP-D), mannan-binding lectin (MBL) and I-NOS in innate immune defense against M. tuberculosis Aims : The present study investigated the role of polymorphisms in three candidate genes encoding Lung surfactant protein D, Mannan binding lectin and Inducible Nitric oxide synthase, in susceptibility and protection to pulmonary tuberculosis. Settings and Design : A case-control association study of SNP's in lung surfactant protein D (SP-D), mannan-binding lectin (MBL) and I-NOS with pulmonary tuberculosis in Indian population was carried out. This involved sequencing of all the coding exons of lung surfactant protein D (SP-D) , while, exon 1 (collagen region) and exon 4 (carbohydrate recognition domain) of mannan-binding lectin (MBL) and exons 2, 8 and 16 of I-NOS and their flanking intronic regions for single nucleotide polymorphisms in DNA samples isolated from 30 pulmonary tuberculosis patients and 30 controls of Indian population. Statistical analysis: Various allele frequencies were calculated using online two by two table (home.clara.net/sisa/). Odds ratio and P values were calculated at 95% confidence interval (CI). Results : A total of fourteen single nucleotide polymorphisms (5 in SP-D , 5 in MBL and 4 in I-NOS ) were observed of which four (G459A SP-D , G274T I-NOS , G1011A and T357G MBL ) have not been reported earlier. Four single nucleotide polymorphisms viz. G459A of exon 7 of SP-D ( P =0.00, odds ratio (OR) = 4.96, 2.18 P = 0.00 or= 3.85 1.66 P =0.00 or=4.04, 2.20< OR<7.42) and G274T of intron 16 of I-NOS ( P =0.00 or=4.46, 2.40 Conclusion: The present study has led to identification of 4 SNP's in SP-D , MBL and I-NOS associated with pulmonary tuberculosis in Indian population.