Virologic and Immunologic Events in Hilar Lymph Nodes During Simian Immunodeficiency Virus Infection - Development of Polarized Inflammation

Abstract

Lymphoid tissues are sites of soluble and cell-associated antigen sampling of peripheral tissues, and they are key compart- ments for the generation of cellular and humoral immune responses. Hilar lymph nodes (HiLNs), which drain the lungs, were examined to understand the effects of simian immunodeficiency virus (SIV) infec- tion on this compartment of the immune system. Histologic and messenger RNA (mRNA) expression profiling approaches were used to determine the numbers, types, and distributions of SIV viral RNA+ cells and to identify differentially expressed genes in HiLNs during SIV infection. SIV RNA+ cells were found to be primarily CD682 and localized to paracortical and medullary regions early in infection, whereas they resided mainly in paracortex during AIDS. As SIV infection progressed, CXCL9, CXCL10, interferon-g, and Toll-like receptor 3 levels all increased. In contrast, CCL19 increased early in infection but decreased during AIDS, whereas CCL21 decreased progressively throughout infection. Finally, local levels of cellular activation were increased throughout infection. Taken together, these findings indicate that SIV infection leads to an inflammatory envi- ronment in lung-draining lymph nodes that is characterized by type 1 cytokines and chemokines and likely has an impact on the nature and strength of immune responses to pulmonary pathogens.