Long-term efficient control of SIV infection in macaques is associated with an intact intestinal barrier
Corresponding Author
Maria Daskalaki
Unit of Infection Models, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Correspondence
Maria Daskalaki, Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Goettingen, Germany.
Email: [email protected]
Search for more papers by this authorBerit Neumann
Unit of Infection Models, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorAntonina Klippert
Unit of Infection Models, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorKerstin Mätz-Rensing
Unit of Infection Pathology, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorFranz-Josef Kaup
Unit of Infection Pathology, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorChristiane Stahl-Hennig
Unit of Infection Models, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorCorresponding Author
Maria Daskalaki
Unit of Infection Models, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Correspondence
Maria Daskalaki, Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Goettingen, Germany.
Email: [email protected]
Search for more papers by this authorBerit Neumann
Unit of Infection Models, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorAntonina Klippert
Unit of Infection Models, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorKerstin Mätz-Rensing
Unit of Infection Pathology, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorFranz-Josef Kaup
Unit of Infection Pathology, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorChristiane Stahl-Hennig
Unit of Infection Models, Leibniz Institute for Primate Research, German Primate Center, Goettingen, Germany
Search for more papers by this authorAbstract
Hallmarks of SIV infection are early depletion of gut CD4 T cells and diminished intestinal integrity. Comprehensive studies on colon biopsies of SIV-infected macaques efficiently controlling infection revealed that in contrast to viremic and failing controllers, elite controllers show preserved CD4 T cells, and low viral load, apoptosis, and inflammation.
Supporting Information
| Filename | Description |
|---|---|
| jmp12294-sup-0001-TableS1.docxWord document, 42.7 KB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Shedlock DJ, Silvestri G, Weiner DB. Monkeying around with HIV vaccines: using rhesus macaques to define ‘gatekeepers’ for clinical trials. Nat Rev Immunol. 2009; 9: 717-728.
- 2Weiler A, May GE, Qi Y, Wilson N, Watkins DI. Polymorphisms in eight host genes associated with control of HIV replication do not mediate elite control of viral replication in SIV-infected Indian rhesus macaques. Immunogenetics. 2006; 58: 1003-1009.
- 3Heise C, Vogel P, Miller CJ, Halsted CH, Dandekar S. Simian immunodeficiency virus infection of the gastrointestinal tract of rhesus macaques. Functional, pathological, and morphological changes. Am J Pathol. 1993; 142: 1759-1771.
- 4Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004; 200: 749-759.
- 5Estes JD, Harris LD, Klatt NR, et al. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog. 2010; 6: e1001052.
- 6Marchetti G, Tincati C, Silvestri G. Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev. 2013; 26: 2-18.
- 7Estes JD. Enhancing immune responses to limit chronic immune activation during SIV. J Clin Invest. 2012; 122: 1611-1614.
- 8Klippert A, Bleyer M, Sauermann U, et al. Lymphocryptovirus-dependent occurrence of lymphoma in SIV-infected rhesus macaques with particular consideration to two uncommon cases of non-Hodgkin's lymphoma. Primate Biol. 2016; 3: 65-75.
10.5194/pb-3-65-2016 Google Scholar
- 9Schultheiss T, Stolte-Leeb N, Sopper S, Stahl-Hennig C. Flow cytometric characterization of the lymphocyte composition in a variety of mucosal tissues in healthy rhesus macaques. J Med Primatol. 2011; 40: 41-51.
- 10Neumann B, Klippert A, Raue K, Sopper S, Stahl-Hennig C. Characterization of B and plasma cells in blood, bone marrow, and secondary lymphoid organs of rhesus macaques by multicolor flow cytometry. J Leukoc Biol. 2015; 97: 19-30.
- 11Klippert A, Stolte-Leeb N, Neumann B, et al. Frequencies of lymphoid T-follicular helper cells obtained longitudinally by lymph node fine-needle aspiration correlate significantly with viral load in SIV-infected rhesus monkeys. J Med Primatol. 2015; 44: 253-262.
- 12Schultheiss T, Schulte R, Sauermann U, Ibing W, Stahl-Hennig C. Strong mucosal immune responses in SIV infected macaques contribute to viral control and preserved CD4+ T-cell levels in blood and mucosal tissues. Retrovirology. 2011; 8: 24.
- 13Hazenberg MD, Otto SA, van Benthem BH, et al. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS. 2003; 17: 1881-1888.
- 14van Asten L, Danisman F, Otto SA, et al. Pre-seroconversion immune status predicts the rate of CD4 T cell decline following HIV infection. AIDS. 2004; 18: 1885-1893.
- 15Mohri H, Bonhoeffer S, Monard S, Perelson AS, Ho DD. Rapid turnover of T lymphocytes in SIV-infected rhesus macaques. Science. 1998; 279: 1223-1227.
- 16Boasso A, Hardy AW, Anderson SA, Dolan MJ, Shearer GM. HIV-induced type I interferon and tryptophan catabolism drive T cell dysfunction despite phenotypic activation. PLoS One. 2008; 3: e2961.
- 17Blaschitz C, Raffatellu M. Th17 cytokines and the gut mucosal barrier. J Clin Immunol. 2010; 30: 196-203.
- 18Dandekar S, George MD, Baumler AJ. Th17 cells, HIV and the gut mucosal barrier. Curr Opin HIV AIDS. 2010; 5: 173-178.
- 19Brenchley JM. Mucosal immunity in human and simian immunodeficiency lentivirus infections. Mucosal Immunol. 2013; 6: 657-665.
