Open Access Research article

Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia

Li Zhou1, Rejane Rua15, Thomas Ng2, Valentina Vongrad1, Yung S Ho1, Carolyn Geczy3, Kenneth Hsu3, Bruce J Brew4 and Nitin K Saksena1*

Author Affiliations

1 Retroviral Genetics Division, Center for Virus Research, Westmead Millennium Institute, Westmead Hospital, The University of Sydney, Westmead, NSW 2145, Sydney, Australia

2 Department of Anatomical Pathology, ICPMR, Westmead Hospital, Westmead, NSW 2145. Sydney, Australia

3 Inflammatory Diseases Research Unit, School of Medical Sciences, University of NSW, Sydney, NSW, 2052, Australia

4 Department of Neurology, St. Vincent's Hospital, Darlinghurst, Sydney, Australia

5 Ecole Normale Superieure, 45 Rue Ulm, 75005 Paris, France

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BMC Infectious Diseases 2009, 9:192  doi:10.1186/1471-2334-9-192

Published: 2 December 2009

Abstract

Background

HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.

Methods

To study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24), anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation). Statistical analysis was performed with SPSS 12.0 with Student's t test and ANOVA.

Results

Overall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures.

Conclusion

Strong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.