Early mediators involved in NKT cell recruitment and liver pathology during C. albicans infection”

RENNA MS; PARAJE G; FIGUEREDO M; CORREA SG; SOTOMAYOR CE

Córdoba

Congreso; VII Latin American Congress of Immunology.; 2005

Early during Candida albicans infection the composition of intrahepatic lymphoid population changes and NKT cells are selectively recruited to the liver with a significant increase after two days of infection. We explored, at local level, the kinetic (Days 1/2/3) of gene expression of pro-inflammatory cytokines and chemokines involved in the NKT cell recruitment in animals infected(Ca) and infected and exposed simultaneously to stress(CaS). On D1, we found in both groups a significantly higher level of mRNA transcripts of IL-1b and IL-6(p<0.05); on D2, Ca group up regulated IL-1b, IL-6, and TNF-a transcripts, while CaS rats only increased transcripts for IL-1b and TNF-a(p<0.05). On D3 transient expression of TNF-a was observed only in Ca group. NKT cells respond to CCL2, CCL4, CXCL8 and IL18. In the liver homogenates we found CCL4 transcripts early after the infection(D1), with a sustained and significant expression of CCL2 and CXCL8 on D2 post infection(p<0.05). On D2, decreased expression of IL-18 mRNA was also observed(p<0.05).  In agreement with previous in vivo results(D2), coculture of C.albicans with purified intrahepatic lymphocytes demonstrated up regulation of Fas-L and TLR2 (FACS/Immunocytochemistry). The kinetic profile of proinflammatory cytokines and chemokines plays an important role in the recruitment of NKT cells that participate in the pathogenesis of the fungal infection. Stress modulate this phenomenon