INTRODUCTION

In addition to its role on mineral metabolism, vitamin D has pleiotropic effects on the control of cell proliferation and on the modulation of immune responses [1-3]. Following the activation of vitamin D precursors in the skin by the exposure to sunlight and their biochemical transformation in the liver, vitamin D acquires full active form after been converted to 1-α-25-dihydroxyvitamin D3 (1,25(OH)₂D3) by the kidney enzyme 25-hydroxyvitamin D3 1-α-hydroxylase (CYP27B1) [4].

Although the immunomodulatory response triggered by active vitamin D was first reported more than 25 years ago, a growing body of experimental evidence has been obtained in the last decade, supporting a key role of vitamin D in the control of both innate and acquired immune responses [6-8]. Both CYP27B1 and VDR are expressed by several immune cells, such as macrophages (MAC), dendritic cells (DC) and lymphocytes. This allows these cells to synthesize and respond to vitamin D in an autocrine/paracrine circuit involved in the modulation of the immune response [6]. The active vitamin D hormone stimulates the innate immune response in MAC and DC, while at the same time acts to squelch any excessive reaction in the adaptive immune response to the antigen. These contrasting effects confer to the vitamin D endocrine system, a central role in the modulation of the immune responses, being responsible of a proper and well-dimensioned response.

In the present review we have emphasized the involvement of vitamin D on infectious diseases, and specifically on HIV infection and disease progression to AIDS. A potential role of vitamin D on HIV infection has been previously considered, either evaluating sun light exposure [9] or taking into consideration HIV infected patients characterized by vitamin D insufficiency [10-14]. A growing body of evidence supports the role of vitamin D as a protection factor in intracellular pathogen infection, such as mycobacterium, through activation of innate immune response [15], despite vitamin D has been found detrimental in Leishmania infection by interfering with key functions of interferon (IFN)-γ activated macrophages [16]. In addition, direct effects of vitamin D promoting HIV replication have been described [17,18] and associated studies of VDR gene polymorphism seem to indicate that gene variants that hamper VDR-mediated activity are associated with susceptibility to infection and disease progression to AIDS [19- 22].