Our Faculty : Primary Faculty

Becky Adkins, Ph.D.

Immunity in Early Life
Newborns and infants are commonly highly susceptible to microbial pathogens. Developmental regulation of immune cell function almost certainly contributes importantly to this sensitivity. The overall aims of the laboratory are to identify the ways in which neonatal and infant immune cells differ from adult cells, to learn how these differences contribute to susceptibility to infection in early life, and to discover the mechanisms underlying these developmental differences in immune function.

Intestinal Pathogens in Early Life
Human infants and young children are highly susceptible to infectious agents. This sensitivity is shared with murine neonates and infants; a great number of model systems have demonstrated that neonatal and infant mice and rats are much more susceptible to microbial infections than are their adult counterparts. In striking contrast, we recently observed that murine newborns (7 day old) are highly resistant to the Gram-negative enteropathogen Yersinia enterocolitia, when exposure occurs via the natural, oral route. Furthermore, animals infected as neonates develop immunological memory, becoming resistant to re-infection in later life. This is the only example among experimental animal models in which neonates are highly resistant to both initial and secondary pathogen exposure. Mechanistic studies have established that innate phagocytes, notably neutrophils, are key players in the heightened resistance. Recent results demonstrate that adaptive responses, involving both B and T cell components, also contribute importantly to neonatal resistance. Thus, Y. enterocolitica may be unique in eliciting highly protective responses from both the innate and adaptive immune systems in neonates. We are using this novel system to understand the potential of the neonatal intestinal immune system. Moreover, we are using this system to identify the Y. enterocolitica factors that promote robust protective immunity in neonates with the goal of utilizing this information to develop potent oral pediatric vaccines.

We have recently expanded our studies with gastrointestinal infections in early life using the murine specific pathogen Citrobacter rodentium. C. rodentium infection of mice is considered to be a faithful model of human infection with enteropathogenic E. coli (EPEC). EPEC infection of infants is a major global health burden. Notably, EPEC infection comprises the highest risk for infectious death in infants. Most infants, however, survive the infection but, during the first year of life, experience multiple cycles of infection associated with poor adaptive immunity. Using high or low dose infection of mouse infants (14 day old), we have developed a murine pediatric model for both of these scenarios in human infants. We are currently studying the immunological basis for (a) the extreme susceptibility of infants to infectious death and (b) the failure of adaptive immunity to prevent repeated infections.

Thus, we are striving to understanding the dynamic interaction of host and enteropathogen in early life. These studies may provide major insights into both prophylactic and therapeutic interventions in pathological pediatric intestinal infection.

Research Profile
Pubmed Profile