Showing papers by "Suresh Mahalingam published in 2010"

Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes.

Abstract: Summary A wide range of microorganisms can replicate in macrophages, and cell entry of these pathogens via non-neutralising IgG antibody complexes can result in increased intracellular infection through idiosyncratic Fcγ-receptor signalling. The activation of Fcγ receptors usually leads to phagocytosis. Paradoxically, the ligation of monocyte or macrophage Fcγ receptors by IgG immune complexes, rather than aiding host defences, can suppress innate immunity, increase production of interleukin 10, and bias T-helper-1 (Th1) responses to Th2 responses, leading to increased infectious output by infected cells. This intrinsic antibody-dependent enhancement (ADE) of infection modulates the severity of diseases as disparate as dengue haemorrhagic fever and leishmaniasis. Intrinsic ADE is distinct from extrinsic ADE, whereby complexes of infectious agents with non-neutralising antibodies lead to an increased number of infected cells. Intrinsic ADE might be involved in many protozoan, bacterial, and viral infections. We review insights into intracellular mechanisms and implications of enhanced pathogenesis after ligation of macrophage Fcγ receptors by infectious immune complexes.

Pulmonary infection of mice with human metapneumovirus induces local cytotoxic T-cell and immunoregulatory cytokine responses similar to those seen with human respiratory syncytial virus

Abstract: Human metapneumovirus (hMPV), is a major cause of upper and lower respiratory tract infection in infants, the elderly and immunocompromised individuals. Virus-directed cellular immunity elicited by hMPV infection is poorly understood, in contrast to the phylogenetically and clinically related pathogen human respiratory syncytial virus (hRSV). In a murine model of acute low.er respiratory tract infection with hMPV, we demonstrate the accumulation of IFN-gamma producing CD8+ T cells in the airways and lungs at day 7 post-infection, associated with cytotoxic T lymphocytes (CTL) directed to an epitope of the M2-1 protein. This CTL immunity was accompanied by increased pulmonary expression of Th-1 cytokines IFN-gamma and IL-12, and anti-viral (IFN-beta) cytokines, as well as chemokines Mip-1alpha, Mip-1beta, Mig, IP-10, CX3CL 1. There was also a moderate increase in Th2-type cytokines cytokines IL-4 and IL-10 compared to uninfected mice. At twenty-one days post-infection, a strong CTL response could be recalled from the spleen. A similar pattern of CTL induction to the homologous M2-1 CTL epitope of hRSV, and of cytokine/chemokine induction, was observed following infection with hRSV, highlighting similarities in the cellular immune response between the two related pathogens.