Depletion of alveolar macrophages exerts protective effects in pulmonary tuberculosis in mice.
Mycobacterium tuberculosis bacilli are intracellular organisms that reside in phagosomes of alveolar macrophages (AMs). To determine the in vivo role of AM depletion in host defense against M. tuberculosis infection, mice with pulmonary tuberculosis induced by intranasal administration of virulent M. tuberculosis were treated intranasally with either liposome-encapsulated dichloromethylene diphosphonate (AM(-) mice), liposomes, or saline (AM(+) mice). AM(-) mice were completely protected against lethality, which was associated with a reduced outgrowth of mycobacteria in lungs and liver, and a polarized production of type 1 cytokines in lung tissue, and by splenocytes stimulated ex vivo. AM(-) mice displayed deficient granuloma formation, but were more capable of attraction and activation of T cells into the lung and had increased numbers of pulmonary polymorphonuclear cells. These data demonstrate that depletion of AMs is protective during pulmonary tuberculosis.
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. j.c.leemans@amc.uva.nl
J C
JC
Leemans
N P
NP
Juffermans
S
S
Florquin
N
N
van Rooijen
M J
MJ
Vervoordeldonk
A
A
Verbon
S J
SJ
van Deventer
T
T
van der Poll
D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016516:CD4-CD8 Ratio; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology; D002469:Cell Separation; D004002:Clodronic Acid / Q000008:administration & dosage; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007165:Immunosuppression Therapy / Q000379:methods*; D008081:Liposomes / Q000008:administration & dosage; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis; D012965:Sodium Chloride / Q000008:administration & dosage; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014373:Tuberculin / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*
D016207:Cytokines; D008081:Liposomes; D014373:Tuberculin; D004002:Clodronic Acid; D012965:Sodium Chloride