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Cose, S.

Publications and source records attributed to Cose, S..

2 recordsLinked to original sources

Human postmortem studies reveal tissue-specific differences amongst TB-patient groups

If we are to break new grounds in TB research, we need to have a complete understanding of what is occurring at the site of infection in humans. Postmortem studies give us an opportunity to compare TB-involved and -uninvolved tissues, in both diseased and non-diseased individuals. We examined the feasibility of carrying out a postmortem study in Mulago and Kiruddu National Referral Hospitals in Uganda, to determine whether we could use immune cells collected postmortem for immunological studies. We report that we can consent the Next-of-Kin, perform postmortem procedures and process tissues within 8 hours of death, and that immune cells remain viable and functional up to 14 hours after death. We found subtle differences in T cell subsets within TB groups. We found a depletion of the CD4 CD69+CD103+ T cell subset in the lungs and BAL, which was associated with HIV, and that the CD8 CD69+CD103- T cell subset was depleted in BAL only, and was associated with TB. Our data show overall changes Tissue Resident Memory T cells within, and between, TB-infected and TB-uninfected human lungs. SummaryO_LICoroner led postmortem studies are possible in Uganda, samples processed within 8 hours from death C_LIO_LICells from samples collected postmortem are viable and functional C_LIO_LIHIV associated depletion of CD4 CD69+/CD103+ T cell subset in lungs and BAL C_LIO_LICD8 CD69+/CD103- depletion in BAL associated with TB C_LI

immunology↗

Mycobacterium tuberculosis infection boosts B cell responses to unrelated pathogens

Antigens from Mycobacterium tuberculosis (M.tb), have been shown to stimulate human B cell responses to unrelated recall antigens in vitro. However, it is not known whether natural M.tb infection or whether vaccination with the related species, Mycobacterium bovis BCG, has a similar effect. This study investigated the effects of M.tb infection and BCG vaccination on B cell responses to heterologous pathogen recall antigens. Antibodies against several bacterial and viral pathogens were quantified by ELISA in 68 uninfected controls, 62 individuals with latent TB infection (LTBI) and 107 active pulmonary TB (APTB) cases, and 24 recently BCG-vaccinated adolescents and naive controls. Antibody avidity was investigated using surface plasmon resonance and B cell ELISPOT assays were used to measure plasmablast and memory B cell responses (MBC) in APTB cases and healthy donor controls. APTB was associated with higher levels of antibodies to tetanus toxoid (TT), diphtheria toxoid, respiratory syncytial virus, measles virus and Kaposis sarcoma herpesvirus, compared to uninfected controls. Vaccination with BCG did not alter levels of antibodies against heterologous pathogens. TT-specific antibody avidity was increased in APTB and the ratio of TT-specific plasmablasts to MBCs in the APTB cases was 7:1. M.tb infection boosts serological memory to heterologous pathogens in human subjects and this process may be driven by polyclonal activation of memory B cells.\n\nSignificanceMycobacterium tuberculosis (M.tb) has potent immunostimulatory properties and has been used in adjuvant preparations to improve vaccine responses in animals. This study shows that natural M.tb infection in humans is associated with increased antibody and B cell recall responses to heterologous pathogens. This data suggests a potential role for M.tb antigens in immunotherapies designed to maintain antibody immunity to diverse infections.

immunology↗