Identification of iNKT follicular helper cells at early stages of T cruzi infection

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017. Buenos Aires, Argentina. 13 al 17 de Noviembre de 2017; 2017

Sociedades Argentinas de Biociencias, entre ellas Sociedad Arg de Inmunología.

Identification of iNKT follicular helper cells at early stages of T cruzi infection Laura Almada1, Facundo Fiocca Vernengo1, Cristian G Beccaria1, Carolina L Montes1, Eva V Acosta-Rodriguez1, Adriana Gruppi1.1 Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA, Córdoba, Argentina.Invariant natural killer T cells (iNKT) are innate T cells wich express semi-invariant T cell receptors. They recognize both endogenous and exogenous lipid antigens presented by CD1d and they rapidly produce cytokines following activation. It has been described that iNKT cells exert a variety of effector functions developing Th1, Th2 and Th17-like phenotype. Recent data showed that iNKT cells could also acquire a Tfh-like phenotype, migrate into the Germinal Center (GC) and sustain B cell responses. It is interesting to note that an exquisite support of GC may actually represent a fundamental mechanism to fine-tune the type and magnitude of antigen-specific antibody responses and that NKTfh could potentially represent a new player in this landscape. The aim of our work was to evaluate the presence and potential role of iNKT in GC response in T. cruzi infection. For that, C57BL/6 mice were infected with 5000 trypomastigotes of T. cruzi Tulahuen strain and the kinetic of iNKT and Tfh was evaluated at different days post-infection (dpi) by flow cytometry. iNKT cells were identified by CD3int expression and binding to α-GalCer-loaded CD1d tetramers. Tfh were characterized by the co-expression of CD3, CD4, ICOS, PD-1 and CXCR5. At 4dpi, we observed that a substantial proportion of iNKT undergo Tfh-like phenotype defined by the co-expression of ICOS, PD-1 and CXCR5, compared to uninfected controls (p<0,05). Interestingly, this population of NKTfh decreased significantly at 7dpi (p<0,05) suggesting a potential role in the early stages of infection. In contrast, Tfh cells, who were almost absent at early stages of the infection, increased in number and frequency at 15dpi (p<0,05). Remarkably, iNKT evidenced high expression of CD335 and CD160 (which may be involved in NKT cell activation and function) and produce IL-4 at 4dpi. This work extends our understanding of the potential contribution of iNKT cell in humoral immune response to T cruzi