No impact of helminth coinfection in patients with smear positive tuberculosis on immunoglobulin levels using a novel method measuring Mycobacterium tuberculosis-specific antibodies.

Helminth/tuberculosis (TB)-coinfection can reduce cell-mediated immunity against Mycobacterium tuberculosis (Mtb) and increase disease severity, although the effects are highly helminth species dependent. Mtb have long been ranked as the number one single infectious agent claiming the most lives. The only licensed vaccine for TB (BCG) offers highly variable protection against TB, and almost no protection against transmission of Mtb. In recent few years the identification of naturally occurring antibodies in humans that are protective during Mtb infection has reignited the interest in adaptive humoral immunity against TB and its possible implementation in novel TB vaccine design. The effects of helminth/TB coinfection on the humoral response against Mtb during active pulmonary TB are however still unclear, and specifically the effect by globally prevalent helminth species such as Ascaris lumbricoides, Strongyloides stercoralis, Ancylostoma duodenale, Trichuris trichiura. Plasma samples from smear positive TB patients were used to measure both total and Mtb-specific antibody responses in a Peruvian endemic setting where these helminths are dominating. Mtb-specific antibodies were detected by a novel approach coating ELISA-plates with a Mtb cell-membrane fraction (CDC1551) that contains a broad range of Mtb surface proteins. Compared to controls without helminths or TB, helminth/TB coinfected patients had high levels of Mtb-specific IgG (including an IgG1 and IgG2 subclass response) and IgM, which were similarly increased in TB patients without helminth infection. These data, indicate that helminth/TB coinfected have a sustained humoral response against Mtb at the level of active TB only. More studies on the species-specific impact of helminths on the adaptive humoral response against Mtb using a larger sample size, and in relation to TB disease severity, are needed.

Helminth Antigen Exposure Enhances Early Immune Control of Mycobacterium tuberculosis in Monocytes and Macrophages.

Helminth and Mycobacterium tuberculosis (Mtb) coinfection is common and suggested to influence the risk of developing active tuberculosis (TB). It is known that helminths in contrast to TB induce a strong Th2 response in the host. However, the direct impact of helminth antigen exposure on host immunity against TB is largely unknown. Our aim was to explore the effects of helminth antigen exposure on the early immune control of Mtb in monocytes and macrophages. Ascaris lumbricoides (ASC) and Schistosoma mansoni (SM) protein antigens were used to study the immediate effect of helminth antigen exposure in monocytes, on monocyte-to-macrophage differentiation, or mature macrophages, in the control of virulent Mtb H37Rv. Pre-exposure of peripheral blood mononuclear cells reduced Mtb growth in monocytes, especially with SM, but no Th1/Th2 cytokines or activation markers indicated involvement of T cells. Monocytes exposed before maturing into macrophages reduced Mtb growth in macrophages (ASC), and pre-exposure of mature macrophages reduced (ASC) or kept Mtb growth at control levels (SM). This in vitro model shows how helminth infection directly affects the monocyte-macrophage axis at an early stage before cell-mediated immunity develops. During acute helminth coinfection or when helminth antigen concentration is elevated at the site of Mtb infection, these helminths provide an enhanced control and killing of Mtb owing to the direct stimulatory effect of helminth antigens on phagocytic cells.

Modulating Inflammation in Monocytes Using Capillary Fiber Organic Electronic Ion Pumps.

An organic electronic ion pump (OEIP) delivers ions and drugs from a source, through a charge selective membrane, to a target upon an electric bias. Miniaturization of this technology is crucial and will provide several advantages, ranging from better spatiotemporal control of delivery to reduced invasiveness for implanted OEIPs. To miniaturize OEIPs, new configurations have been developed based on glass capillary fibers filled with an anion exchange membrane (AEM). Fiber capillary OEIPs can be easily implanted in proximity to targeted cells and tissues. Herein, the efficacy of such a fiber capillary OEIP for modulation of inflammation in human monocytes is demonstrated. The devices are located on inflammatory monocytes and local delivery of salicylic acid (SA) is initiated. Highly localized SA delivery results in a significant decrease in cytokine (tumor necrosis factor alpha and interleukin 6) levels after lipopolysaccharide stimulation. The findings-the first use of such capillary OEIPs in mammalian cells or systems-demonstrate the utility of the technology for optimizing transport and delivery of different therapeutic substances at low concentrations, with the benefit of local and controlled administration that limits the adverse effect of oral/systemic drug delivery.