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

TYPE II GRANULOMA INDUCED BY SCHISTOSOMA MANSONI EGGS IN 5-
LIPOXYGENASE KNOCKOUT MICE
GABRIEL TOFFOLI DA SILVA (IC) (1) ; MILENA SOBRAL ESPÍNDOLA (PG)
(1,2) ; CAROLINE FONTANARI (T) (1) ; ALYNE FÁVERO GALVÃO (T) (1) ; OLINDA
MARA B. TREVILATO (T) (2) ; ELAINE MEDINA FLORIANO (T) (2) ; VANDERLEI
RODRIGUES (2) ; SIMONE GUSMÃO RAMOS (2) ; LÚCIA HELENA FACCIOLI
(1) ; FABIANI GAI FRANTZ (1) .
(1). Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, SP
(2). Faculdade de Medicina de Ribeirão Preto, USP, SP.
Introduction: In the experimental model to study type 2 granulomas, mice are
inoculated intraperitoneally and challenged intravenously with eggs of
Schistosoma mansoni, previously isolated from liver of chronically infected
animals. In this model, granulomas are developed in the lungs 4 days after
challenge, involving mainly mononuclear cells and little collagen deposition, with
an initial induction of TH1-type immune responses (production of IFN-γ, with low
levels of IL-4 and IL-13). This response is transient and passes to a TH2 profile,
with lesions containing mononuclear cells, eosinophils and fibroblasts, with
significant collagen deposition, characteristic of granulomas type II. Lipoxins
and leukotrienes are lipid mediators derived from arachidonic acid metabolites
via the 5-lipoxygenase (5LO) pathaway. However, until now no one knows how
these mediators are involved in the induction of type II granuloma. In this study,
we aim to investigate how type II granulomas develop in mice knockout of the 5lipoxygenase
gene (5LO-KO).
Methods and Results: Wild-type or 5LO-KO mice were inoculated
intraperitoneally with 3000 eggs of S. mansoni, and 14 days later, mice were
challenged intravenously with 3000 eggs of the parasite. Four, eight and sixteen
days after intravenous administration of the eggs, the animals were killed for the
assessment of pulmonary granuloma formation, determining size, cellular
composition, and fibrosis formation by histopathology techniques and
production of cytokines and chemokines by ELISA. Apparently, compared to
WT mice, 5LO-KO animals had fewer granulomas, in despite of its larger size.
Regarding the production of cytokines, the absence of 5LO relates to a high
rate of TGF-β after 4 days of intravenous inoculation and a lower production of
IL-13 compared to WT in the same period.
Conclusion: This high production of TGF-β in 5LO-KO mice in the first days
can be related to the control of the granulomas number. Furthermore, the lower
production of others cytokines and chemokines in 5LO-KO compared to WT can
be related to the uncontrolled growth of granulomas in the lung.
Financial support: FAPESP