Many aspects of the complex interaction between HIV and the human immune system remain elusive. Our objective is to study these interactions, focusing on the specific roles of Langerhans cells (LCs) in HIV infection. In patients infected with HIV, a large amount of virus is associated with LCs in lymphoid tissue. To assess the influence of LCs on HIV viral dynamics during antiretroviral therapy, we present and analyse a stochastic model describing the dynamics of HIV, T cells, and LCs interactions under therapeutic intervention in vivo and show that LCs play an important role in enhancing and spreading initial HIV infection. We perform sensitivity analyses on the model to determine which parameters and/or which interaction mechanisms strongly affect infection dynamics. 1. Introduction HIV is a devastating human pathogen that causes serious immunological diseases in humans around the world. The virus is able to remain latent in an infected host for many years, allowing for the long-term survival of the virus and inevitably prolonging the infection process [1]. The location and mechanisms of HIV latency are under investigation and remain important topics in the study of viral pathogenesis. Given that HIV is a blood-borne pathogen, a number of cell types have been proposed to be the sites of latency, including resting memory + T cells, peripheral blood monocytes, dendritic cells (including Langerhans cells) and macrophages in the lymph nodes, and haematopoietic stem cells in the bone marrow [2]. This study updates the latest advances in the study of HIV interactions with Langerhans cells and highlights the potential role of these cells as viral reservoirs and the effects of the HIV-host-cell interactions on viral pathogenesis. Despite advances in our understanding of HIV and the human immune response in the last 25 years, much of this complex interaction remains elusive. T cells are targets of HIV and are also important for the establishment and maintenance of an adaptive immune response [3]. The skin and mucosa are the first line of defense of the organism against external agents, not only as a physical barrier between the body and the environment but also as the site of initiation of immune reactions. The immunocompetent cells which act as antigen-presenting cells are Langerhans cells (LCs). Infection of LCs by HIV is relevant to several reasons. Firstly, LCs of mucosal epithelia may be among the first cells to be infected following mucosal HIV exposure and, secondly, LCs may serve as a reservoir for continued infection of T cells, especially in lymph
References
[1]
C. M. Coleman and L. Wu, “HIV interactions with monocytes and dendritic cells: viral latency and reservoirs,” Retrovirology, vol. 6, no. 1, article 51, 2009.
[2]
C. St. Gelais, C. M. Coleman, J.-H. Wang, and L. Wu, “HIV-1 nef enhances dendritic cell-mediated viral transmission to CD4+ T cells and promotes T-cell activation,” PLoS ONE, vol. 7, no. 3, Article ID e34521, 2012.
[3]
I. B. Hogue, S. H. Bajaria, B. A. Fallert, S. Qin, T. A. Reinhart, and D. E. Kirschner, “The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infection,” Journal of General Virology, vol. 89, no. 9, pp. 2228–2239, 2008.
[4]
E. Ramazzotti, A. Marconi, M. C. Re et al., “In vitro infection of human epidermal Langerhans' cells with HIV-1,” Immunology, vol. 85, no. 1, pp. 94–98, 1995.
[5]
J. Paul Zoeteweij and A. Blauvelt, “HIV-dendritic cell interactions promote efficient viral infection of T cells,” Journal of Biomedical Science, vol. 5, no. 4, pp. 253–259, 1998.
[6]
D. Schmitt and C. Dezutter-Dambuyant, “Epidermal and mucosal dendritic cells and HIV1 infection,” Pathology Research and Practice, vol. 190, no. 9-10, pp. 955–959, 1994.
[7]
C. Dezutter-Dambuyant, “In vivo and in vitro infection of human langerhans cells by HIV-1,” in Dendritic Cells in Fundamental and Clinical Immunology, J. Banchereau and D. Schmitt, Eds., vol. 378, pp. 447–452, Springer, New York, NY, USA, 1995.
[8]
N. K. Saksena, B. Wang, L. Zhou, M. Soedjono, Y. Shwen Ho, and V. Conceicao, “HIV reservoirs in vivo and new strategies for possible eradication of HIV from the reservoir sites,” HIV/AIDS, vol. 2, pp. 103–122, 2010.
[9]
W. S. Hlavacek, N. I. Stilianakis, and A. S. Perelson, “Influence of follicular dendritic cells on HIV dynamics,” Philosophical Transactions of the Royal Society B, vol. 355, no. 1400, pp. 1051–1058, 2000.
[10]
D. McDonald, “Dendritic cells and HIV-1 trans-infection,” Viruses, vol. 2, no. 8, pp. 1704–1717, 2010.
[11]
N. Romani, P. M. Brunner, and G. Stingl, “Changing views of the role of langerhans cells,” Journal of Investigative Dermatology, vol. 132, no. 3, pp. 872–881, 2012.
[12]
C. R. Rinaldo, “HIV-1 trans infection of CD4+ t cells by professional antigen presenting cells,” Scientifica, vol. 2013, Article ID 164203, 30 pages, 2013.
[13]
W. R. Mbogo, L. S. Luboobi, and J. W. Odhiambo, “Stochastic model for in-host HIV dynamics with therapeutic intervention,” ISRN Biomathematics, vol. 2013, Article ID 103708, 11 pages, 2013.
[14]
T. Mugwagwa, Mathematical models of coreceptor usage and a dendritic cell-based vaccine during HIV-1 infection [Ph.D. thesis], University of Cape Town, 2005.
[15]
J.-F. Arrighi, M. Pion, E. Garcia et al., “DC-SIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from dendritic cells to T cells,” Journal of Experimental Medicine, vol. 200, no. 10, pp. 1279–1288, 2004.
[16]
C. Chougnet and S. Gessani, “Role of gp120 in dendritic cell dysfunction in HIV infection,” Journal of Leukocyte Biology, vol. 80, no. 5, pp. 994–1000, 2006.
[17]
A. Granelli-Piperno, A. Golebiowska, C. Trumpfheller, F. P. Siegal, and R. M. Steinman, “HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 20, pp. 7669–7674, 2004.
[18]
W. R. Mbogo, L. S. Luboobi, and J. W. Odhiambo, “Mathematical model for HIV and CD4+ cells dynamics in vivo,” International Electronic Journal of Pure and Applied Mathematics, vol. 6, no. 2, pp. 83–103, 2013.
