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

DECREASED ACTIVATION OF MONOCYTES IN PATIENTS WITH
MULTIBACILLARY LEPROSY
GIOVANA BERGHEME FRANCISCON 1 ; SARA PASSOS 1 ; TAIS CAMPOS 1 ;
MAYUME SHIBUYA 1 ; EDGAR M. CARVALHO 1,2 ; PAULO MACHADO 1,2 AND
LUCAS P. CARVALHO 1,2,3 .
1 Serviço de Imunologia, Universidade Federal da Bahia; 2 Instituto de Ciência e
Tecnologia – Doenças Tropicais (INCT-DT); 3 Instituto de Ciências da Saúde
(ICS), Universidade Federal da Bahia.
Introduction: Leprosy is a chronic granulomatous disease caused by
Mycobacterium leprae, which has tropism for peripheral nerves and skin. While
patients with multibacillary (MB) disease do not mount type 1 immune response
facilitating the multiplication of Mycobacterium, paucibacillary (PB) individuals
produce IFN-gamma in response to M. leprae antigens, what control bacteremia
but causes immunopathology. Downregultion of type 1 immune response
observed in MB patients may be due to decreased antigen presentation and /or
co-stimulation. In the present study we aimed to evaluate the frequency and
degree of activation of subsets of monocyte in peripheral blood of patients with
MB and PB forms of leprosy, prior and after treatment.
Methods and Results: Peripheral blood mononuclear cells from MB and PB
patients were obtained; frequency and degree of activation of subsets of
monocyte were determined ex-vivo by flow cytometry, prior and after treatment.
There was no difference between frequency of monocyte subsets between MB
and PB patients prior to treatment. However, analysis of co-stimulatory
molecules expression in monocytes reveiled that the non-classical
(CD14 dim CD16 + ) population of monocytes from MB patients had a significant
decrease in CD86 expression when compared to the ones from PB individuals.
CD86 expression in monocytes from MB patients was restored after
polychemotherapy. To test whether Mycobacterium antigens could
downregulate CD86 expression, we treated monocytes from helathy individuals
with M. leprae antigens and assesed MHC class II and CD86 expression in
these cells. We found IL-10-independent decrease in CD86 expression 8h after
treatment with M. leprae antigens.
Conclusions: These data suggest that high bacteremia observed in MB
patients contribute directly to downregulation of CD86 expression in monocytes
from these individuals. Future functional analysis shall be performed to test
whether decrease in CD86 expression leads to low Th1 cytokines production in
MB patients.
Financial Support: INCT-DT and CNPq.