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

PARTICIPATION OF CYTOKINES AND CHEMOKINES IN HOST
SUSCEPTIBILITY TO INFECTION BY Legionella longbeachae
GRAZIELE ZENARO MANIN 1 ; JULIANA ISSA HORI 1 ; LILIANA MOURA
MASSIS 1 ; DARIO SIMÕES ZAMBONI 1 .
(1). Department of Cellular and Molecular Biology, School of Medicine of
Ribeirão Preto, University of São Paulo (FMRP/USP).
Introduction: Bacteria from Legionella genus are recognized as etiological
agents of Legionnaires‟ disease or legionellosis, a severe and atypical
pneumonia that is an important cause of mortality and morbidity worldwide. The
main Legionella species that causes legionellosis is L. pneumophila and the
disease caused by it has been extensively studied. However, there is little
information regarding the mechanisms by which the immune system eliminates
the pulmonary infection caused by L. longbeachae, despite its higher
importance in some countries. In the present study, we aimed to analyze if IL-
17R, IL-23 and CCR5 are related with susceptibility or resistance to L.
longbeachae, since IL-17R ligand and CCR5 and IL-23 have been described as
factors involved in neutrophil recruitment, histological characteristic observed in
lungs of infected individuals.
Methods and Results: To verify the importance of IL-17R, IL-23 and CCR5 to
infection with L. longbeachae, we intranasally infected mice deficient in these
molecules (n=10) and analyzed their survival. When challenged with L.
longbeachae (MOI 10 6 /mouse), IL-17R-deficient mice and CCR5- deficient mice
(both in C57BL/6 background) had significantly higher survival rates than Wildtype
mice (respectively 50% and 75% vs 20%), while IL-23-deficient mice had
survival rate similar to Wild-type (10% vs 20%). We also analyzed the bacterial
numbers in the lungs of infected mice after 48 hours post-infection and found a
strong replication of the bacteria in the lungs of all mice tested: IL-17R (4x10 7 ±
2x10 7 bacteria per lung) and CCR5-deficient mice (4x10 7 ±3x10 7 bacteria per
lung) and Wild-type (7x10 7 ±2x10 7 bacteria per lung).
Conclusion: These results indicate that IL-17R and CCR5 are molecules
associated with susceptibility to L. longbeachae in experimental model of
Legionnaires‟ disease. Additional experiments should be done to clarify their
specific role in this disease.
Financial support: FAPESP, INCTV/CNPq, FAEPA, CAPES.