LY9 AGONIST REDUCES GERMINAL CENTER AND PLASMABLAST RESPONSE IN TRYPANOSOMA CRUZI INFECTION: ROLE OF INKT AND MZB CELLS

ALMADA, LAURA; BECCARIA, CRISTIAN GABRIEL; FIOCCA VERNENGO, FACUNDO; GAZZONI, YAMILA; ENGEL, PABLO; BOCCARDO, SANTIAGO; ACOSTA RODRIGUEZ, EVA V.; MONTES, CAROLINA LUCÍA; GRUPPI, ADRIANA

Mar del Plata

Congreso; SAIC SAI SAFIS 2018; 2018

Ly9 is an inhibitory receptor, a SLAM family member, present on all lymphocytes. Its highest expression is found on innate-like lymphocytes such as iNKT and MZ B cells. Treatment of mice with a Ly9 agonist selectively depletes splenic MZ and B1 B cells, reduces iNKT cells number and impairs IL-4 and IFN-ɣ production by iNKT. It was reported that iNKT cells promote the early seeding of germinal center (GC) reaction to infections and that MZ B cells could be also involved in GC reaction due to their location and high expression of CD1d. The aim of our work is to evaluate the effect of a Ly9 agonist on the GC and extrafollicular response in T cruzi infection. For this, 1 day before intraperitoneal infection with 5000 trypomastigotes of T cruzi (Tulahuén) or PBS (control), C57BL/6 mice were intraperitoneally injected with anti-Ly9 (Ly9-mice) or with control isotype. Splenic lymphocytes were evaluated by FACS. Five days post-treatment, Ly9-mice exhibited a strong reduction in the frequency of MZB cells (B220+ CD19+ CD21hi CD23lo) and iNKT cells (CD3int α-GalCer-CD1d-Tetramer+ B220-) were diminished in numbers and activation (quantified by CD69 expression) compared with controls (p?0.05). At 15 days post-infection (dpi), Ly9-mice had a lower frequency and number of GC B cells (B220+ CD19+ FAS+ GL7+) and Plasmablasts (B220lo CD138int) than infected controls (p?0.05).Finally, we analyzed the phenotype and functions of iNKT cells at early stages of infection. T cruzi infection increased the frequency of IL-4- and IFN-ɣ-producing iNKT cells and triggered CXCR5 and FAS-L expression in a percentage of iNKT, at 4 dpi. In this context, iNKT and MZB cells could be involved in the GC and extrafollicular responses in T cruzi infection. Further studies are needed to test our hypothesis.