Dr. Laetitia Aerts was awarded the 2016 ACEA Biosciences xCELLigence Research Grant for investigating the impact of interleukin-22 on mycobacterium tuberculosis growth inside macrophages.
Worldwide nearly 10 million new cases of mycobacterium tuberculosis (TB) are diagnosed each year, leading to 1.5 million deaths. Despite many decades of TB research, an effective vaccine for this scourge has remained elusive. This is due, in part, to the complexity of TB’s interactions with the host immune system. Most individuals develop an appropriate immune response to TB infection but still fail to clear the bacterium.
To date, most studies of the cellular immune response to TB have focused on Th1-mediated responses (including interferon gamma), which activate macrophages to kill the bacteria. However, based on a number of findings published in the literature, Laetitia Aerts (a Postdoctoral Researcher in the Laboratory of Vaccinology and Mucosal Immunity at Université Libre de Bruxelles) has suggested that interleukin-22 (IL-22) may be a key player in TB pathogenesis. To help elucidate the largely unstudied function(s) of IL-22 in TB pathogenesis, Dr. Aerts has proposed exposing TB-infected monocyte-derived macrophages to autologous IL-22 secreting lymphocytes in co-culture experiments, and evaluating both the health/behavior of the macrophages and their intracellular cache of TB bacteria. While including anti-IL-22 antibody in the growth media will be used to assess the specific effect of IL-22, a transwell device will determine whether direct interactions between macrophages and lymphocytes are important. For all of these experiments xCELLigence® Real-Time Cell Analysis (RTCA) will be used to track the macrophage response (proliferation, morphology, and cell-substrate attachment quality). Subsequently, the macrophages will be isolated directly from the RTCA microtiter plate and lysed to release intact intracellular TB bacteria – which can then be cultured to quantify the total intracellular bacterial load. Unlike end-point assays wherein the macrophages would be destroyed by the analysis process, Aerts noted that using RTCA will enable her to conduct “the [macrophage] cytotoxicity assay and the mycobacterial growth inhibition assays using the same cells.”
On the basis of its potential for having high impact on human health, and the strength of its experimental design, Dr. Aerts’ grant proposal entitled “Microbicidal and Cytotoxic Effect of IL-22 During Tuberculosis Infection” was selected by ACEA Biosciences, from a large pool of applicants, as the winner of the 2016 xCELLigence Research Grant. This grant is aimed at helping early career scientists achieve their research goals by providing them free access to RTCA technology. Dr. Aerts will receive an xCELLigence RTCA instrument, consumables, and consultation for a period of 6 months.
“We are thrilled to support this young research scientist in her endeavor to better understand this devastating infectious disease,” noted Yama Abassi, Ph.D., Vice President of ACEA Biosciences. “ACEA is committed to working closely with scientists throughout the world to help accelerate research towards eradicating diseases like TB.”
ACEA’s xCELLigence® Real Time Cell Analysis (RTCA) instruments utilize gold microelectrodes embedded in the bottom of microtiter wells to non-invasively monitor the status of adherent cells using the principle of cellular impedance. In short, cells act as insulators – impeding the flow of an alternating microampere electric current between electrodes. This impedance signal is measured automatically, at an interval defined by the user, and provides an extremely sensitive readout of cell number, cell size/shape, and cell-substrate attachment strength. ACEA is currently accepting grant applications for 2017.