Receptor for advanced glycation end products is protective during murine tuberculosis.
The development of active tuberculosis after infection with Mycobacterium tuberculosis is almost invariably associated with a persistent or transient state of relative immunodeficiency. The receptor for advanced glycation end products (RAGE) is a promiscuous receptor that is involved in pulmonary inflammation and infection. To investigate the role of RAGE in tuberculosis, we intranasally infected wild-type (Wt) and RAGE deficient (RAGE(-/-)) mice with live virulent M. tuberculosis. While lungs of uninfected Wt mice expressed RAGE, in particular on endothelium, M. tuberculosis pneumonia was associated with an enhanced pulmonary expression of RAGE. Lung inflammation was increased in RAGE(-/-) mice, as indicated by histopathology, percentage of inflamed area, lung weight and cytokine and chemokine levels. In addition, lung lymphocyte and neutrophil numbers were increased in the RAGE(-/-) mice. RAGE(-/-) mice had modestly higher mycobacterial loads in the lungs after 3 weeks but not after 6 weeks of infection. Moreover, RAGE(-/-) mice displayed more body weight loss and enhanced mortality. In summary, pulmonary RAGE expression is increased during tuberculosis. In addition, these data suggest that RAGE plays a beneficial role in the host response to pulmonary tuberculosis.
Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. M.A.vanZoelen@amc.uva.nl
Marieke A D
MA
van Zoelen
Catharina W
CW
Wieland
Gerritje J W
GJ
van der Windt
Sandrine
S
Florquin
Peter P
PP
Nawroth
Angelika
A
Bierhaus
Tom
T
van der Poll
D000818:Animals; D058491:Bacterial Load; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D009504:Neutrophils / Q000276:immunology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
D018925:Chemokines; D016207:Cytokines; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic