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Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection
- Source :
- Brazilian Journal of Infectious Diseases, Vol 21, Iss 1, Pp 42-50 (2017), Brazilian Journal of Infectious Diseases v.21 n.1 2017, Brazilian Journal of Infectious Diseases, Brazilian Society of Infectious Diseases (BSID), instacron:BSID, Brazilian Journal of Infectious Diseases, Volume: 21, Issue: 1, Pages: 42-50, Published: FEB 2017
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Objectives: Three decades after HIV recognition and its association with AIDS development, many advances have emerged – especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. Methods: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (MGM-CSF+IFN-γ) or alternative (MIL-4+IL13) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. Results: The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Conclusion: Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections. Keywords: HIV-1, Innate immune response, HAART, Macrophages
- Subjects :
- CD4-Positive T-Lymphocytes
Innate immune response
0301 basic medicine
Chemokine
HAART
Lipopolysaccharide Receptors
lcsh:QR1-502
HIV Infections
CD8-Positive T-Lymphocytes
lcsh:Microbiology
Pathogenesis
0302 clinical medicine
Antiretroviral Therapy, Highly Active
Medicine
Macrophage
Chemokine CCL5
Medicine(all)
biology
Viral Load
Treatment Outcome
Infectious Diseases
Acute Disease
Adult
Microbiology (medical)
CD14
CD4-CD8 Ratio
Peripheral blood mononuclear cell
Statistics, Nonparametric
lcsh:Infectious and parasitic diseases
03 medical and health sciences
Acquired immunodeficiency syndrome (AIDS)
Humans
lcsh:RC109-216
Tumor Necrosis Factor-alpha
business.industry
Interleukins
Macrophages
medicine.disease
Virology
Chemokine CXCL10
TLR2
030104 developmental biology
Case-Control Studies
Chronic Disease
Immunology
HIV-1
biology.protein
TLR4
business
030215 immunology
Subjects
Details
- ISSN :
- 14138670
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- The Brazilian Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....4facbf6ba02e3b8a6907d98ec6f91661
- Full Text :
- https://doi.org/10.1016/j.bjid.2016.10.004