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

P. BRASILIENSIS AND MANNAN USE MR, CR3 AND TLR4 TO INTERACT
WITH MACROPHAGES BUT INDUCE OPPOSITE ACTIVATION PROFILES
IN MACROPHAGES OF RESISTANT AND SUSCEPTIBLE MICE
FERIOTTI CLAUDIA (1); CALICH VERA LUCIA GARCIA (1)
(1) University of São Paulo
Introduction: In addition to alpha1,3 glucan, mannan and mannan-linked
proteins are expressed in the outer layer of Paracoccidioides brasiliensis
yeasts. Mannosyl residues are recognized by several membrane pathogen
recognition receptors (PRRs), such as the mannose receptor (MR), complement
receptor 3 (CR3) and toll-like receptor 4 (TLR4) on macrophage membranes.
The aim of this study was to clarify the role of these receptors in the interaction
between P. brasiliensis and macrophages from resistant (A/J) and susceptible
(B10.A) mice. Methods and Results: Therefore, the phagocytic, fungicidal and
secretory abilities of macrophages were evaluated in the presence of mannan
and antibodies against MR, CR3 and TLR4. In addition, the mRNA expression
of SOCS3, a protein associated with M1 macrophages; was also evaluated. We
verified that mannan and anti-MR antibody exert antagonistic effects, the former
increasing and the latter decreasing the killing ability and nitric oxide production
of macrophages. In addition, the specific blockade of MR, CR3 and TLR4
impaired fungal recognition and modulated the production of cytokines.
Interestingly, both mannan and P. brasiliensis induced the production of IL-12
by B10.A macrophages, whereas TNF-α, IL-6 and TGF-β were produced by A/J
cells. Normal B10.A and A/J macrophages expressed different levels of
phagocytic and non-phagocytic PRRs. Mannan and P. brasiliensis infection led
to decreased expression of MR and TLR2 on A/J macrophages, whereas CR3,
TLR4 and TLR2 were reduced on B10.A cells. Accordingly the expression of
SOCS3 mRNA was significantly higher in B10.A macrophages indicating a
preferential M1 profile. Conclusion: macrophages appear to use MR, CR3 and
TLR4 to interact with P. brasiliensis; however, the resulting divergent activation