|ODERM ATT, BERNHARD|
Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/15/2006
Publication Date: 11/1/2006
Citation: Harris, N.L., Spoerri, I., Schopfer, J.F., Nembrini, C., Merky, P., Massacand, J., Urban Jr, J.F., Lamarre, A., Burki, K., Odermatt, B., Zinkernagel, R.M., Macpherson, A.J. 2006. Mechanisms of neonatal mucosal antibody protection. Journal of Immunology. 177(9):6256-6262.
Interpretive Summary: The immune system functions optimally when both its innate and acquired components are activated in immune competent individuals. Newborns (neonates) have the disadvantage of being immune incompetent because the immune system must be activated by helpful micro organisms (commensals) and protected from harmful micro organisms (pathogens) before they can mature and demonstrate resistance. Mammalian species differ in the passive transfer of immune cells and antibodies from their mothers. Some species receive mother’s antibodies in utero, others only after birth through the intestines, and others through both mechanisms. Nevertheless, antibodies passively taken from the mother ensure optimum health as the immune system in the neonate is developing. We are exploring models to test the use of helpful probiotic bacteria which can enhance and improve immune development. Our model is primarily the use of pigs because of their similarity to humans, but other models using mice can be helpful to test hypotheses before further study in pigs and humans. The current report demonstrates that the intestine is protective from harmful micro and macro organisms due to antibodies from the mother that comes directly to the intestine through the milk as well as transport from the serum to the intestine. This provides a useful target to test the efficacy of probiotics on neonatal responses to infectious agents, and would be of interest to those who study immunity and probiotic effects on health.
Technical Abstract: Following an abrupt transition at birth from the sterile uterus to an environment with abundant commensal and pathogenic microbes, neonatal mammals are protected by maternal antibodies at mucosal surfaces. We show in mice that different antibody isotypes work in distinct ways to protect the neonatal mucosal surface. Secretory IgA acts to limit penetration of commensal intestinal bacteria through the neonatal intestinal epithelium: an apparently primitive process which does not require diversification of the primary natural antibody repertoire. In contrast, neonatal protection against the exclusively luminal parasite Heligmosomoides polygyrus required IgG from primed females. This immune IgG could either be delivered directly in milk or retro transported via FcRn from the neonatal serum into the intestinal lumen to exert its protective effect.