Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Nashwa K Abousamra, Raida S Yahya, Soha I Awad, Hanan Azzam, Gehan Atia and Hatim A El-Baz
Accepted Abstracts: J Clin Cell Immunol
Pneumonia is a major cause of mortality in children under the age of five worldwide resulting in close to 20 percent of all deaths in this age group. Consequently, investigations into the host-pathogen interactions during S. pneumoniae infection are keys to devising strategies towards the development of better vaccines and drugs. To that end in this study it was investigated the role of S. pneumoniae and its antigen pneumococcal surface protein A (PspA) in modulating the expression of the co-inhibitory molecule Programmed Death Ligand -1 (PD-L1) on bone marrow derived dendritic cells (DCs) and the subsequent effects of increased PD-L1 levels on immune responses. PD-L1 is a co-stimulatory molecule that largely induces suppressor responses and causes T cell inactivation and anergy. Obtained data indicates that stimulation of DCs with PspA increases the surface expression of PDL1 in a time and dose dependent manner. Characterization of intracellular signalling molecules indicate that PspA induced expression of PDL1 was dependent on MAPK pathway and routes of calcium influx. While calcium release from intracellular stores positively regulated PDL1 expression, calcium influx from external milieu negatively regulated PDL1 expression. Knockdown of intermediates in the TLR pathway showed that the expression of PDL1 was dependent on MyD88. Knockdown of PD-L1 promoted apoptosis of DCs and increased autophagic responses together with increase in the levels of pro-inflammatory cytokines like IL-12 and IL-6. These results indicate that increased expression of PD-L1 mediated by PspA could be an immune evasion strategy adopted by S. pneumoniae to establish a long term infection. Further characterization of the responses is underway.