Parental occupations and risk for Crohn's disease in children.

BACKGROUND AND OBJECTIVES: Lacunae exist on the identity of specific environmental risk factors that associate with Crohn's disease (CD). We hypothesized that indirect exposures acquired via the parents' occupation may confer susceptibility. METHODS: A case-control study based on children diagnosed with CD (prior to age 20) at a tertiary care gastroenterology clinic in Montreal, Canada was carried out. Population- and hospital-based controls without IBD were selected. Information on occupations held by the parents was acquired from interview. Jobs were coded using the Canadian National Occupational Classification for Statistics. Associations were examined using logistic regression accounting for potential confounders. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated. RESULTS: A total of 466 cases and 335 controls were studied. The mean (±SD) age of the cases (12.4 ± 3.2) was slightly higher than controls (10.5 ± 4.9). Gender and ethnicity were equally distributed between the groups. Logistic regression analysis suggested that children whose fathers worked as retail salespersons/sales clerks [odds ratio (OR) 3.6, 95% confidence interval (CI) 1.2-11.1], and whose mothers worked as administrative secretaries (OR 3.2, 95% CI 1.6-6.4), were more likely to be at risk for CD. Mothers who worked as either early childhood educators (OR 2.3, 95% CI 0.85-6.2) or as clerks (OR 2.8, 95% CI 0.8-9.9) also appeared to confer risks, but these associations were statistically not significant. CONCLUSION: Parental occupations related to 'social mixing' that can potentially enhance exposure to infectious agents, appear to confer higher risk for CD in children.

Differential modulation of CCR5-tropic human immunodeficiency virus-1 transfer from macrophages towards T cells under interleukin-4/interleukin-13 microenvironment.

Macrophages constitute major human immunodeficiency virus type 1 (HIV-1) reservoirs at the mucosal level, and their functional activity is modulated by cytokine environments that could play a role in HIV-1 mucosal spread. As proof of concept, we herein evaluated the modulation of HIV/macrophages interactions associated with two ubiquitous T(h)2 cytokines, namely, interleukin (IL)-4 and IL-13, using the in vitro model of R5-HIV-1 transfer from macrophages to T lymphocytes. Monocyte-derived macrophages differentiated in the presence of IL-4 (M-4) transferred the virus to T cells more efficiently than those differentiated in the presence of interleukin-13 (M-13), likely because to their high capacity to capture and produce HIV-1 and to recruit HIV-1 target T cell. However, M-13 harbored high levels of HIV DNA, similarly to M-4, and secreted HIV-activating factors. Notably, uninfected macrophages recruited HIV-1 target T cells (CCR4(+)IL-13(+) T(h)2 cells and CD4(+)CCR5(+) T cells), indicating their role in facilitating the HIV-1 spread by a passive manner. Strikingly, R5-HIV-1 reprogrammed macrophages toward a T(h)1 secretion pattern. Thus, T(h)2 microenvironment facilitates the emergence of HIV-1 macrophage reservoir and HIV-1 spread. In conclusion, secreted cytokines within mucosae may differentially influence both the HIV-1 production within the mucosal target cells reservoir and its spread thorough the mucosal tissue.

Infection of macrophages and dendritic cells with primary R5-tropic human immunodeficiency virus type 1 inhibited by natural polyreactive anti-CCR5 antibodies purified from cervicovaginal secretions.

Heterosexual contact is the primary mode of human immunodeficiency virus (HIV) type 1 (HIV-1) transmission worldwide. The chemokine receptor CCR5 is the major coreceptor that is associated with the mucosal transmission of R5-tropic HIV-1 during sexual intercourse. The CCR5 molecule is thus a target for antibody-based therapeutic strategies aimed at blocking HIV-1 entry into cells. We have previously demonstrated that polyreactive natural antibodies (NAbs) from therapeutic preparations of immunoglobulin G and from human breast milk contain NAbs directed against CCR5. Such antibodies inhibit the infection of human macrophages and T lymphocytes by R5-tropic isolates of HIV in vitro. In the present study, we demonstrate that human immunoglobulins from the cervicovaginal secretions of HIV-seronegative or HIV-seropositive women contain NAbs directed against the HIV-1 coreceptor CCR5. Natural affinity-purified anti-CCR5 antibodies bound to CCR5 expressed on macrophages and dendritic cells and further inhibited the infection of macrophages and dendritic cells with primary and laboratory-adapted R5-tropic HIV but not with X4-tropic HIV. Natural anti-CCR5 antibodies moderately inhibited R5-tropic HIV transfer from monocyte-derived dendritic cells to autologous T cells. Our results suggest that mucosal anti-CCR5 antibodies from healthy immunocompetent donors may hamper the penetration of HIV and may be suitable for use in the development of novel passive immunotherapy regimens in specific clinical settings of HIV infection.

Differential modulation of human lactoferrin activity against both R5 and X4-HIV-1 adsorption on epithelial cells and dendritic cells by natural antibodies.

Human lactoferrin (Lf) is an iron binding glycoprotein that is present in several mucosal secretions. Many biological functions have been ascribed to Lf. In the present study, we showed that Lf limited specifically adsorption of R5- and X4-HIV-1-free particles on endometrial epithelial HEC-1A cells, by inhibiting virus adsorption on heparan-sulfated proteoglycans. But, Lf did not interfere with both R5 and X4-HIV transcytosis. We showed also the efficacy of Lf in preventing R5 and X4-HIV capture by dendritic cells. Conversely, we demonstrated that Lf-reacting natural Abs (NAbs) present within i.v. Ig-enhanced HIV attachment on dendritic cells by forming HIV-Lf-NAbs. HIV particles were able to directly interact with Lf following its interaction with NAbs. We also found Lf-reacting natural Abs within cervicovaginal secretions, suggesting the existence of Lf-NAbs complexes in women genital tract in vivo. In conclusion, this study highlights Lf as a potent microbicides and reports new function for NAbs within the genital compartment that may compartment that may abolish the inhibitory activity of microbicide compounds. Thus, we proposed a model in which Lf would appear as a double-edged sword that could have beneficial or detrimental effects depending on both cellular and molecular environments. This study highlights the use of Lf derivates as microbicide candidates to limit such interferences.