MAP of F1 and V antigens from Yersinia pestis astride innate and adaptive immune response

• Immunization with F1 and V MAP significantly increased DC maturation in mouse model.
• Expression of TLR2 and TLR4 on macrophages was markedly increased by F1 and V MAP.
• Resulting in increased cytokine production. Possible role in linking innate and adaptive immunity.

Yersinia pestis, a causative agent of plague, has a plethora of armors to fight against major components of innate immunity and survive within host cells. Dendritic cells and macrophages are important antigen presenting cells for effective immune response. This report is focused on the changes in DC activation and TLR2 and TLR4 expression on macrophages induced by MAP of F1 and V antigens of Y. pestis. F1 and V MAPs bear potential synthetic T and B cell epitopes from F1 and V protein respectively. We evaluated these parameters in DC's isolated from spleen and lamina propria and macrophages isolated from peritoneal lavage of mice after intranasal immunization. F1 MAP and V MAP significantly increased the expression of CD80 and CD86 on CD11c+ dendritic cells isolated from spleen and lamina propria as well as intracellular IL-12 levels. Similarly, in macrophages derived from peritoneal cavity, the above formulation enhanced TLR2 and TLR4 expression. Again after in vitro stimulation with F1 and V MAP these macrophages produced significantly high IL12 and TNFα. The study clearly indicates involvement of DC and macrophages for efficient antigen presentation to immune cells. From this study we conclude that F1MAP and VMAP ameliorate innate immune mechanism. These two synthetic constructs exert their effect via TLR2 and TLR4, leading to the production of proinflammatory cytokines by macrophages and are able to increase DC activation, that could be helpful in generation of adaptive immunity as well as is important strong immune response.