immunology of infectious and parasitic diseases - XXXVII Congress ...

AREA: IMMUNOLOGY OF INFECTIOUS AND PARASITIC DISEASES (ID)
TOLL-LIKE RECEPTOR 4 MEDIATE IL-6 AND TNF- PRODUCTION
DURING PLACENTAL MALARIA.
Aramys Silva dos Reis 1 ; Renato Barboza 1 ; Niels Olsen Saraiva Câmara 2 ; Silvia
Beatriz Boscardin 1 ; Sabrina Epiphanio 3 & Claudio Romero Farias Marinho 1
1 Departamento de Parasitologia, ICB, Universidade de São Paulo, São Paulo,
Brasil; 2 Departamento de Imunologia, ICB, Universidade de São Paulo, São
Paulo, Brasil; 3 Departamento de Ciências Biológicas, Universidade Federal de
São Paulo, Diadema, Brasil.
Introduction: Immune system activation induced by Plasmodium ssp. during
pregnancy leads a production of pro-inflammatory cytokines that may culminate
in a range of complications affecting both mother and fetus. It has been
described that Toll-like receptor 4 (TLR4) recognize components of Plasmodium
sp. and affect the host immune response. The objective of this work was to
evaluate the effects of TLR4 on development of placental malaria induced by P.
berghei NK65. Methods & Results: To verify the effects of TLR4, we infected
pregnant TLR4 -/- and C57BL/6 (WT) mice with P. berghei NK65 on the 13 th
gestational day. To obtain the spleen cells, at 19 th gestational day the animals
were killed and their spleen were removed and processed. Analysis of spleen
cell population of infected WT mice by flow cytometry showed an increase of T
CD4 + cells, B cells (CD19 + ), granulocytes (Gr1 + ) and NK1.1 + when compared
with non-infected mice. However, analysis of TLR4 -/- strain not showed
difference between infected and non-infected mice. Moreover, TLR4 -/- mice cell
populations of both groups were similar to the control group (non-infected WT).
Next, we evaluated serum cytokine production from infected and non-infected
pregnant mice by cytokine beads array (CBA). CBA analysis showed that
infected WT and TLR4-/- mice presented an increase of pro-inflammatory
cytokines IL-6, TNF-alfa and IFN-gamma when compared with the controls.
Comparison of infected mice groups of both strains showed that WT mice
presented a huge increase of IL-6 and TNF-alfa, but the IFN-gamma production
was not different. To evaluate the effect of inflammatory process on the
placenta, we conducted a histopathological analysis. Our results showed that
only infected WT mice presented a decrease of vascular space (indicative of
placental injure). Conclusion: The results presented here suggest that TLR4 is
important for the development of placental malaria due an inflammation process
mediated by the IL-6 and TNF-alfa.
Financial support: FAPESP & Capes/CNPq