Written by Stefan Tuomanen

This month we have the pleasure of featuring Assistant Professor Beatriz León-Ruiz in our faculty spotlight. Dr. León-Ruiz has been an influential member of UAB Microbiology since 2012, first as a postdoctoral fellow and then joining the faculty a year later. Since then, she has made numerous advances in understanding the roles dendritic cells play in directing the T Helper 2 (Th2)-driven immune response; in particular differentiating the behavior of these cells in infants compared to adults.

It is in detailing these differences that Dr. León-Ruiz hopes to better prevent unwanted, and potentially fatal, allergic reactions in infants, who are already three to four times more susceptible to allergens than adults. A Spanish native of the La Rioja region, Dr. León-Ruiz spent the early part of her academic career in Madrid. After completing her Bachelor’s degree at Complutense University, she moved to the Autónoma University where she earned her PhD in Microbiology and Immunology. After her first year as a post-doc, she moved from Autónoma to the Trudeau Institute in New York and began her relationship under PI Frances E. Lund. The two then moved to the University of Roche and finally put their roots down here at UAB. “There is a nice structure here in the states” Dr. León-Ruiz said about the differences between European and US academia. “In Spain, you can get a very good college education and technical experience, but the opportunities for PhDs and afterwards are very difficult. People here can really set you up to succeed in that regard.” And succeed she has.

As a researcher Dr. León-Ruiz has always been attracted to the core tenets of the scientific method and scientific thinking, and it is this respect and diligence that she feels has allowed her to excel. She has spent most of her academic career with her microscope on dendritic cells (DC). These cells, found largely in the skin and intestinal tract, are the first cells that recognize and interact with pathogens in the humoral and cellular immune response. They process the antigen’s materials and present them on their surface acting as the translators between antigens and T-cells. Th2 cells in particular are naturally induced to fight parasites but, interestingly, also against allergens or dust mites. This triggers an allergic reaction. Curiously, although the Th2-immune response will be triggered universally when a host encounters a parasite, there is a great deal of variance in the triggering of the response by non-pathogenic factors across hosts. Dr. León-Ruiz and her colleagues want to understand this variance and believe that the answer lies, at least in part, with the responses of DCs of infants.

Obviously infant immune systems are different than adult immune systems in numerous manners but, for Dr. León-Ruiz, it is the infant immune system’s lower response to pathogens that is of particular interest. Simply put, an infant has yet to build up a substantial cellular memory of common pathogens. As they are exposed to pathogens and allergens simultaneously, a child’s immune system responds less to microbes which in turn upregulates their response to associated allergens. Therefore, to prevent allergic responses, it is important to build up adequate cellular memory. Some children don’t develop this as well as others. In a 2014 paperpublished in The Journal of Experimental Medicine, Dr. León-Ruiz and her colleagues detailed the role of dendritic cells in programming CD8 T-cells in response to influenza-specific epitopes. Specifically they found that even though “The commitment of naive CD8 T cells to effector or memory cell fates can occur after a single day of antigenic stimulation” (León, et al. 2014), dendritic cells can still present the antigens for some time after the acute infection. It is this persistent presentation that was shown to allow for stronger cell memory programming of the T-cells. The more numerous and longer the antigen-presenting DCs persisted, the greater the fitness of the resulting CD8 T-cells. The question still remains why DCs seem to present antigens in such different manners and for different lengths of time in infants than compared to a more standardized way in adults. It is not yet known if the specific order in which your immune system is challenged plays a factor but in preliminary investigations, Dr. León-Ruiz has found that lipopolysaccharides, a key component of the membrane of Gram-negative bacteria, is strongly linked to the development of asthma in infants.

In her research in mice, the adult-phenotype DCs develop around the time the mice are weaned from their mother’s milk. This has led her to investigate the role of various factors in a mother’s milk that can either increase or decrease allergic responses in their child. It has been known that the composition of lipids and fatty acids can influence the immune system. But more interestingly, the mother’s allergic susceptibilities can modify these compositions and therefore affect the child. In a pending grant proposal, Dr. León-Ruiz hopes to investigate the immune mechanisms of maternal transmission specifically of allergic asthma susceptibility.

Furthermore, in another pending research grant, Dr. León-Ruiz hopes to investigate the role Pseudomonas aeruginosa, a common Gram-negative bacterium, plays in asthma susceptibility. A pathogen most everyone is exposed to, P. aeruginosa can delve deep into the lungs when one’s immune system is downregulated. It is quite resistant to treatment and can therefore obviously become problematic yet it has been observed in mice that the infection also provides significant resistance to allergic diseases like asthma. Dr. León-Ruiz has already contributed much to the understanding of the relationship between pathogens and allergic reactions. Her lab’s recent works have been published twice in the high impact immunological journal Immunity. Look forward to reading her lab’s upcoming manuscript “Impaired Tumor Necrosis Factor-α-driven dendritic cell activation limits Lipopolysaccharide-induced protection from allergic inflammation in infants” in the journal’s January 2019 issue. Through the continuation of her research, she hopes not only to understand the specific mechanisms (the how of the relationship) but also be able to ideally prevent the development of life-altering and life-threatening allergic diseases.