Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load.
HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb) infection are at significantly greater risk of reactivation tuberculosis (TB) than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV). Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks) had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection.
Diedrich
Collin R
CR
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Mattila
Joshua T
JT
Klein
Edwin
E
Janssen
Chris
C
Phuah
Jiayao
J
Sturgeon
Timothy J
TJ
Montelaro
Ronald C
RC
Lin
Philana Ling
PL
Flynn
Joanne L
JL
D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D015897:Comorbidity; D005434:Flow Cytometry / Q000379:methods; D006099:Granuloma / Q000378:metabolism; D007107:Immune System; D007371:Interferon-gamma / Q000378:metabolism; D008252:Macaca fascicularis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
D000914:Antibodies, Viral; D007371:Interferon-gamma