Persistent pneumocystis colonization leads to the development of chronic obstructive pulmonary disease in a nonhuman primate model of AIDS.
Human immunodeficiency virus (HIV)-infected patients are at increased risk for development of pulmonary complications, including chronic obstructive pulmonary disease (COPD). Inflammation associated with subclinical infection has been postulated to promote COPD. Persistence of Pneumocystis is associated with HIV infection and COPD, although a causal relationship has not been established. We used a simian/human immunodeficiency virus model of HIV infection to study pulmonary effects of Pneumocystis colonization. Simian/human immunodeficiency virus-infected/Pneumocystis-colonized monkeys developed progressive obstructive pulmonary disease characterized by increased emphysematous tissue and bronchial-associated lymphoid tissue. Increased levels of T helper type 2 cytokines and proinflammatory mediators in bronchoalveolar lavage fluid coincided with Pneumocystis colonization and a decline in pulmonary function. These results support the concept that an infectious agent contributes to the development of HIV-associated lung disease and suggest that Pneumocystis colonization may be a risk factor for the development of HIV-associated COPD. Furthermore, this model allows examination of early host responses important to disease progression, thus identifying potential therapeutic targets for COPD.
Shipley
Timothy W
TW
Department of Immunology, Division of Pulmonary, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Kling
Heather M
HM
Morris
Alison
A
Patil
Sangita
S
Kristoff
Jan
J
Guyach
Siobhan E
SE
Murphy
Jessica E
JE
Shao
Xiuping
X
Sciurba
Frank C
FC
Rogers
Robert M
RM
Richards
Thomas
T
Thompson
Paul
P
Montelaro
Ronald C
RC
Coxson
Harvey O
HO
Hogg
James C
JC
Norris
Karen A
KA
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004646:Emphysema / Q000382:microbiology / Q000821:virology; D006678:HIV; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D008173:Lung Diseases, Obstructive / Q000000981:diagnostic imaging / Q000382:microbiology; D008252:Macaca fascicularis; D011010:Pneumocystis / Q000302:isolation & purification / Q000472:pathogenicity*; D011323:Primates; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000382:microbiology / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus; D014057:Tomography, X-Ray Computed
D018925:Chemokines; D016207:Cytokines