Virologic and immunologic events in hilar lymph nodes during simian immunodeficiency virus infection: development of polarized inflammation.

Lymphoid tissues are sites of soluble and cell-associated antigen sampling of peripheral tissues, and they are key compartments 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) infection 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 CD68 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-gamma, 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 environment 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.

Head and neck squamous and thyroid carcinomas: multiplexed Luminex approaches for early detection.

Head and neck cancer (HNC) comprises a broad group of malignancies affecting a number of organs in this anatomical region. The most common histologic type is mucosal squamous cell carcinoma of the head and neck (SCCHN). SCCHN accounts for ∼ 50,000 annual cases of HNC in the US. It is an aggressive disease that has been linked to altered growth factor signaling, immune inflammatory responses and angiogenesis. In addition to mucosal SCCHN, increasing frequency of cancer of the thyroid gland has also been recognized over the past several decades. There is a growing interest in the use of biomarker approaches for the early detection of SCCHN and thyroid cancer. This article provides an overview of SCCHN and thyroid cancer and outlines the rationale and need for the clinical application of multiplexed ELISA-based assays as serum proteomic studies for early detection of cancer. Although thyroid cancer has a generally favorable long-term outcome, its screening and diagnosis pose a challenge due to the prevalence of benign nodular thyroid disease, the rising incidence of thyroid cancer, chronicity and recurrence. In the authors' published studies, it was hypothesized that an expanded panel of biomarkers comprised of cytokines, chemokines, growth factors and other tumor markers, which individually may show some promising correlation with disease status, might provide higher diagnostic power if used in combination. The potential clinical role for using these technologies in follow-up, tumor surveillance to permit early identification of recurrence of SCCHN or thyroid cancer in recurrent disease or second primary tumors is discussed.

Increased expression of interferon-inducible genes in macaque lung tissues during simian immunodeficiency virus infection.

Pulmonary infections and dysfunction are frequent outcomes during the development of immunodeficiency associated with human immunodeficiency virus type 1 (HIV-1) infection, and obtaining a better understanding of the immunologic changes that occur in lungs following HIV-1 infection will provide a foundation for the development of further intervention strategies. We sought here to identify changes in the pulmonary immune environment that arise during simian immunodeficiency virus (SIV) infection of rhesus macaques, which serves as an excellent model system for HIV-1 infection and disease. To examine the gene expression profiles of macaque lung tissues following infection with the pathogenic SIV/DeltaB670 isolate, we performed cDNA microarray hybridizations with lung total RNAs using two commercially available cDNA arrays and a custom-fabricated, immunologically focused macaque cDNA microarray. In situ hybridization and real-time RT-PCR were performed to provide additional analyses of gene expression. Among the genes exhibiting the highest level of induction in lung tissues were the IFN-gamma-inducible chemokines, CXCL10/IP-10 and CXCL9/Mig. In situ hybridization and real-time RT-PCR strongly supported these findings. Correlation analyses revealed that the levels of expression of IFN-gamma, CXCL9/Mig, and CXCL10/IP-10 mRNAs were all strongly positively correlated, and that CXCL10/IP-10 mRNA and Pneumocystis carinii rRNA were positively correlated. Taken together, these findings demonstrate that inflammatory chemokines are among the most differentially expressed mRNAs in macaque lung tissues during systemic SIV infection of rhesus macaques, and provide insight into the complicated events occurring in the lung tissues during HIV-1 infection in humans.