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HIV-1 infection of macrophages dysregulates innate immune responses to Mycobacterium tuberculosis by inhibition of interleukin 10

HIV-1 infection of macrophages dysregulates innate immune responses to Mycobacterium tuberculosis by inhibition of interleukin 10
HIV-1 infection of macrophages dysregulates innate immune responses to Mycobacterium tuberculosis by inhibition of interleukin 10
Human immunodeficiency virus (HIV)–1 and Mycobacterium tuberculosis (Mtb) both target macrophages, which are key cells in inflammatory responses and their resolution. Therefore, we tested the hypothesis that HIV-1 may modulate macrophage responses to coinfection with Mtb. HIV-1 caused exaggerated proinflammatory responses to Mtb that supported enhanced virus replication, and were associated with deficient stimulus-specific induction of anti-inflammatory interleukin (IL)–10 and attenuation of mitogen-activated kinase signaling downstream of Toll-like receptor 2 and dectin-1 stimulation. Our in vitro data were mirrored by lower IL-10 and higher proinflammatory IL-1? in airway samples from HIV-1–infected patients with pulmonary tuberculosis compared with those with non-tuberculous respiratory tract infections. Single-round infection of macrophages with HIV-1 was sufficient to attenuate IL-10 responses, and antiretroviral treatment of replicative virus did not affect this phenotype. We propose that deficient homeostatic IL-10 responses may contribute to the immunopathogenesis of active tuberculosis and propagation of virus infection in HIV-1/Mtb coinfection.
HIV-1, inflammation, interleukin-10, macrophage, tuberculosis
0022-1899
1055-1065
Tomlinson, G.S.
eb9a6abd-eccc-48f1-af4a-5f43d5ab545f
Bell, L.C.K.
c2343212-3f53-48af-9b8b-a369b322418b
Walker, N.F.
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Tsang, J.
1907bf2b-a5e0-4956-9e16-40c7566de383
Brown, J.S.
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Breen, R.
a022d768-05a0-4e4d-885b-dacf3fb9c985
Lipman, M.
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Katz, D.R.
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Miller, R.F.
ceb4cd5c-5633-4326-87ba-701121a9f65f
Chain, B.M.
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Elkington, P.T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Noursadeghi, M.
7ef3936d-5d26-491a-8419-19711866e6cc
Tomlinson, G.S.
eb9a6abd-eccc-48f1-af4a-5f43d5ab545f
Bell, L.C.K.
c2343212-3f53-48af-9b8b-a369b322418b
Walker, N.F.
5f89ac75-7335-4d8a-bc46-f23d5933ac9f
Tsang, J.
1907bf2b-a5e0-4956-9e16-40c7566de383
Brown, J.S.
29625f00-8599-429e-ac65-57fef4579e07
Breen, R.
a022d768-05a0-4e4d-885b-dacf3fb9c985
Lipman, M.
fa64523e-20e5-4f3f-95e0-43a24d50c34a
Katz, D.R.
0d2e6aa1-e60c-4a42-8426-e7521c38e061
Miller, R.F.
ceb4cd5c-5633-4326-87ba-701121a9f65f
Chain, B.M.
a959b50b-a500-4b47-99a7-6af35abeb223
Elkington, P.T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Noursadeghi, M.
7ef3936d-5d26-491a-8419-19711866e6cc

Tomlinson, G.S., Bell, L.C.K., Walker, N.F., Tsang, J., Brown, J.S., Breen, R., Lipman, M., Katz, D.R., Miller, R.F., Chain, B.M., Elkington, P.T. and Noursadeghi, M. (2014) HIV-1 infection of macrophages dysregulates innate immune responses to Mycobacterium tuberculosis by inhibition of interleukin 10. The Journal of Infectious Diseases, 209 (7), 1055-1065. (doi:10.1093/infdis/jit621).

Record type: Article

Abstract

Human immunodeficiency virus (HIV)–1 and Mycobacterium tuberculosis (Mtb) both target macrophages, which are key cells in inflammatory responses and their resolution. Therefore, we tested the hypothesis that HIV-1 may modulate macrophage responses to coinfection with Mtb. HIV-1 caused exaggerated proinflammatory responses to Mtb that supported enhanced virus replication, and were associated with deficient stimulus-specific induction of anti-inflammatory interleukin (IL)–10 and attenuation of mitogen-activated kinase signaling downstream of Toll-like receptor 2 and dectin-1 stimulation. Our in vitro data were mirrored by lower IL-10 and higher proinflammatory IL-1? in airway samples from HIV-1–infected patients with pulmonary tuberculosis compared with those with non-tuberculous respiratory tract infections. Single-round infection of macrophages with HIV-1 was sufficient to attenuate IL-10 responses, and antiretroviral treatment of replicative virus did not affect this phenotype. We propose that deficient homeostatic IL-10 responses may contribute to the immunopathogenesis of active tuberculosis and propagation of virus infection in HIV-1/Mtb coinfection.

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More information

Accepted/In Press date: 3 October 2013
e-pub ahead of print date: 21 November 2013
Published date: 1 April 2014
Keywords: HIV-1, inflammation, interleukin-10, macrophage, tuberculosis
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 359630
URI: https://eprints.soton.ac.uk/id/eprint/359630
ISSN: 0022-1899
PURE UUID: 32ff181d-dd75-4b6c-950b-09fdacde38b5
ORCID for P.T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 08 Nov 2013 09:01
Last modified: 20 Jul 2019 00:41

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Contributors

Author: G.S. Tomlinson
Author: L.C.K. Bell
Author: N.F. Walker
Author: J. Tsang
Author: J.S. Brown
Author: R. Breen
Author: M. Lipman
Author: D.R. Katz
Author: R.F. Miller
Author: B.M. Chain
Author: P.T. Elkington ORCID iD
Author: M. Noursadeghi

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