Production and differentiation of myeloid cells driven by proinflammatory cytokines in response to acute pneumovirus infection in mice.

Respiratory virus infections are often pathogenic, driving severe inflammatory responses. Most research has focused on localized effects of virus infection and inflammation. However, infection can induce broad-reaching, systemic changes that are only beginning to be characterized. In this study, we assessed the impact of acute pneumovirus infection in C57BL/6 mice on bone marrow hematopoiesis. We hypothesized that inflammatory cytokine production in the lung upregulates myeloid cell production in response to infection. We demonstrate a dramatic increase in the percentages of circulating myeloid cells, which is associated with pronounced elevations in inflammatory cytokines in serum (IFN-γ, IL-6, CCL2), bone (TNF-α), and lung tissue (TNF-α, IFN-γ, IL-6, CCL2, CCL3, G-CSF, osteopontin). Increased hematopoietic stem/progenitor cell percentages (Lineage(-)Sca-I(+)c-kit(+)) were also detected in the bone marrow. This increase was accompanied by an increase in the proportions of committed myeloid progenitors, as determined by colony-forming unit assays. However, no functional changes in hematopoietic stem cells occurred, as assessed by competitive bone marrow reconstitution. Systemic administration of neutralizing Abs to either TNF-α or IFN-γ blocked expansion of myeloid progenitors in the bone marrow and also limited virus clearance from the lung. These findings suggest that acute inflammatory cytokines drive production and differentiation of myeloid cells in the bone marrow by inducing differentiation of committed myeloid progenitors. Our findings provide insight into the mechanisms via which innate immune responses regulate myeloid cell progenitor numbers in response to acute respiratory virus infection.

IGRAs--the gateway to T cell based TB diagnosis.

Development of Interferon-Gamma Release Assays (IGRAs) and implementation of their use in clinical practice almost 10 years ago has revolutionised diagnosis of latent tuberculosis (TB) infection (LTBI). The commercially available IGRAs, TSPOT.TB (Oxford Immunotech, Oxford, UK) and QuantiFERON Gold In-Tube (Cellestis, Victoria, Australia), allow detection of TB infection with greater specificity and sensitivity than the tuberculin skin test (TST) and are now recommended for diagnosis of LTBI. The TSPOT.TB assay is a simplified enzyme-linked immunospot assay (ELISpot) that enumerates TB-specific T lymphocytes (T cells) secreting interferon-gamma (IFNγ). In comparison, the QuantiFERON Gold In-Tube assay constitutes an enzyme-linked immunosorbent assay (ELISA) to quantify IFNγ released into blood plasma after incubation of whole blood with TB antigens. Release of IFNγ, as a result of antigen stimulation of TB-specific T cells within blood, is indicative of TB infection. Although IGRAs have significant advantages over the TST in diagnosis of latent TB, they have significant limitations. Discovery of new antigens and advances in methodology for measuring cellular immunity have recently paved the way for novel tests that overcome these limitations. By establishing for the first time technological platforms for T cell based diagnosis in diagnostic service laboratories, IGRAs provide a bridgehead to clinical application of T cell based diagnosis in routine practice.

Investigation of APOE isoforms and the association between APOE E3 and E4 with migraine in the Australian Caucasian population.

Migraine is a debilitating neurovascular disease that is associated with pulsating head pain accompanied by nausea, vomiting, photophobia, phonophobia and sometimes visual sensory disturbances. Because of its role in nitric oxide regulation and interleukin release, apolipoprotein E (APOE) has been suggested to play a role in the migraine pathogenesis pathway. This study evaluated the potential role of three APOE variants in an Australian population and the role that they may play in susceptibility to migraine. The study found no significant association between the tested variants and migraine for any of the APOE variants investigated.