Macaques with Rapid Disease Progression and Simian Immunodeficiency Virus Encephalitis Have a Unique Cytokine Profile in Peripheral Lymphoid Tissues

Abstract

were comparable between animals with rapid (survival, <200 days) or slow/normal (survival, >200 days) disease progression. However, among rapid progressors, the eight animals with SIV encephalitis had a unique cytokine profile (increased IL-2, IL-6, and IFN-␥) that was associated with higher viral loads. These observations provide evidence that host cytokine responses may influence SIV neuropathogenesis independent of disease progression.

Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS

“…49 IL-10 treatment of cultured DCs strongly reduces their immunostimulatory function, associated with inhibition of expression of CD83. 50 Importantly, monkeys with AIDS have been shown to have increased levels of IL-10 RNA in lymph nodes as compared to controls, 51 supporting a role for IL-10 in suppressing IDC activation. Moreover, IL-10 knockout mice have enhanced migration of epidermal LCs from skin in response to contact sensitization, 52 suggesting that increased levels of IL-10 in AIDS may impair LC migration in vivo.…”

Simian Immunodeficiency Virus Infection Alters Chemokine Networks in Lung Tissues of Cynomolgus Macaques

“…46 IL-10 is an anti-inflammatory cytokine and can suppress Th1 lymphocyte responses and activation of macrophages. SIVmac251-infected macaques with AIDS have higher expression of IL-10 mRNA in peripheral lymphoid tissues compared with controls, 47 and individuals with HIV-1 infection have higher circulating IL-10 levels than controls, with the highest levels among patients with AIDS. 48,49 In a murine PCP model, gene therapy with viral IL-10 can reduce tissue inflammation without altering pathogen clearance.…”

Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-γ in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

“…Our findings regarding IFN-␥ induction are consistent with those of previous studies of IFN-␥ induction during HIV-1 and SIV infection. [23][24][25][26][27] It is important to note that although we identified CXCL9/Mig as a differentially expressed chemokine in macaque lymphoid tissues during SIV infection and propose a model for its contribution to immunopathogenesis (see below), other factors likely modulate the immune environment in lymphoid tissues, including the combined effects of multiple chemokines 28 or chemokines and cytokines, 29 as well as chemokine interactions with the extracellular matrix, 30 and require further investigation.…”