Innate and adaptive immune responses during acute M. tuberculosis infection in adult household contacts in Kampala, Uganda.

Contacts of active pulmonary tuberculosis (TB) patients are at risk for Mycobacterium tuberculosis (MTB) infection. Because most infections are controlled, studies during MTB infection provide insight into protective immunity. We compared immune responses of adult household contacts that did and did not convert the tuberculin skin test (TST). Innate and adaptive immune responses were measured by whole blood assay. Responses of TST converters (TSTC) were compared with persistently TST negative contacts (PTST-) and contacts who were TST+ at baseline (TST+). TLR-2, TLR-4, and IFN-γR responses to IFN-γ did not differ between the groups, nor did γδ T cell responses. T cell responses to MTB antigens differed markedly among TSTC, PTST-, and TST+ contacts. Thus, no differences in innate responses were found among the three household contact groups. However, adaptive T cell responses to MTB antigens did differ before and during MTB infection among PTST-, TSTC, and TST+ contacts.

[1]  R. Rojas,et al.  Vdelta2+ gammadelta T cell function in Mycobacterium tuberculosis- and HIV-1-positive patients in the United States and Uganda: application of a whole-blood assay. , 2005, The Journal of infectious diseases.

[2]  P. Small,et al.  Progression to active tuberculosis, but not transmission, varies by Mycobacterium tuberculosis lineage in The Gambia. , 2008, The Journal of infectious diseases.

[3]  C. Harding,et al.  Phosphoantigen Presentation by Macrophages to Mycobacterium tuberculosis-Reactive Vγ9Vδ2+ T Cells: Modulation by Chloroquine , 2002, Infection and Immunity.

[4]  R. Hussain,et al.  Longitudinal Tracking of Cytokines after Acute Exposure to Tuberculosis: Association of Distinct Cytokine Patterns with Protection and Disease Development , 2007, Clinical and Vaccine Immunology.

[5]  R. Rojas,et al.  Vδ2+ γδ T Cell Function in Mycobacterium tuberculosis– and HIV-1–Positive Patients in the United States and Uganda: Application of a Whole-Blood Assay , 2005 .

[6]  M. Newport,et al.  A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. , 1996, The New England journal of medicine.

[7]  A. Aderem,et al.  Toll-like receptors in the induction of the innate immune response , 2000, Nature.

[8]  T. Ottenhoff,et al.  Innate Immunity to Mycobacterium tuberculosis , 2002, Clinical Microbiology Reviews.

[9]  L. Praloran [Classification of pulmonary tuberculosis]. , 1953, Minerva medica.

[10]  C. Harding,et al.  Phosphoantigen presentation by macrophages to mycobacterium tuberculosis--reactive Vgamma9Vdelta2+ T cells: modulation by chloroquine. , 2002, Infection and immunity.

[11]  W. Miller,et al.  Tuberculin reactivity in bacille Calmette-Guérin vaccinated populations: a compilation of international data. , 2006, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[12]  S. Porcelli,et al.  CD1 proteins: targets of T cell recognition in innate and adaptive immunity. , 2000, Reviews in immunogenetics.

[13]  D. Golenbock,et al.  Toll-Like Receptor 2-Dependent Inhibition of Macrophage Class II MHC Expression and Antigen Processing by 19-kDa Lipoprotein of Mycobacterium tuberculosis1 , 2001, The Journal of Immunology.

[14]  R. Adegbola,et al.  Large-scale evaluation of enzyme-linked immunospot assay and skin test for diagnosis of Mycobacterium tuberculosis infection against a gradient of exposure in The Gambia. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  B. Bloom,et al.  Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. , 1999, Science.

[16]  F. Martini,et al.  γδ T Cells Cross-Link Innate and Adaptive Immunity in Mycobacterium tuberculosis Infection , 2011, Clinical & developmental immunology.

[17]  P. Schierloh,et al.  Mycobacterium tuberculosis-Induced Gamma Interferon Production by Natural Killer Cells Requires Cross Talk with Antigen-Presenting Cells Involving Toll-Like Receptors 2 and 4 and the Mannose Receptor in Tuberculous Pleurisy , 2007, Infection and Immunity.

[18]  B. Graovac [Classification of pulmonary tuberculosis]. , 1956, Tuberkuloza.

[19]  R. Hussain,et al.  Biomarker Changes Associated with Tuberculin Skin Test (TST) Conversion: A Two-Year Longitudinal Follow-Up Study in Exposed Household Contacts , 2009, PloS one.

[20]  K. McAdam,et al.  Risk factors for tuberculosis infection in sub-Saharan Africa: a contact study in The Gambia. , 2003, American journal of respiratory and critical care medicine.

[21]  M. Pai,et al.  False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? , 2006, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[22]  Yan Zhang,et al.  Immune Complex/Ig Negatively Regulate TLR4-Triggered Inflammatory Response in Macrophages through FcγRIIb-Dependent PGE2 Production1 , 2009, The Journal of Immunology.

[23]  R. Rojas,et al.  Human immunity to M. tuberculosis: T cell subsets and antigen processing. , 2003, Tuberculosis.

[24]  W. Boom,et al.  Immune correlates of acute Mycobacterium tuberculosis infection in household contacts in Kampala, Uganda. , 2006, The American journal of tropical medicine and hygiene.

[25]  D. Guwatudde,et al.  Tuberculosis in household contacts of infectious cases in Kampala, Uganda. , 2003, American journal of epidemiology.

[26]  D. Golenbock,et al.  Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. , 1999, Journal of immunology.

[27]  G. Schoolnik,et al.  Immunogenicity of Novel DosR Regulon-Encoded Candidate Antigens of Mycobacterium tuberculosis in Three High-Burden Populations in Africa , 2009, Clinical and Vaccine Immunology.

[28]  C. Stein,et al.  Genetic Epidemiology of Tuberculosis Susceptibility: Impact of Study Design , 2011, PLoS pathogens.

[29]  R. Brown,et al.  Bacille Calmette-Guérin vaccination enhances human gamma delta T cell responsiveness to mycobacteria suggestive of a memory-like phenotype. , 1998, Journal of immunology.

[30]  Sang-Nae Cho,et al.  γδ T Cells in Immunity Induced by Mycobacterium bovis Bacillus Calmette-Guérin Vaccination , 2004, Infection and Immunity.

[31]  M. Hatherill,et al.  The Tuberculin Skin Test versus QuantiFERON TB Gold® in Predicting Tuberculosis Disease in an Adolescent Cohort Study in South Africa , 2011, PloS one.

[32]  J. Belisle,et al.  Definition of Mycobacterium tuberculosis culture filtrate proteins by two-dimensional polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and electrospray mass spectrometry , 1997, Infection and immunity.

[33]  D. Menzies Interpretation of repeated tuberculin tests. Boosting, conversion, and reversion. , 1999, American journal of respiratory and critical care medicine.

[34]  D. Havlir,et al.  Selective expansion of human gamma delta T cells by monocytes infected with live Mycobacterium tuberculosis. , 1991, The Journal of clinical investigation.

[35]  K. Takeda,et al.  Innate Immune Effectors in Mycobacterial Infection , 2011, Clinical & developmental immunology.

[36]  Alimuddin Zumla,et al.  Myobacterium tuberculosis Induces Selective Up-Regulation of TLRs in the Mononuclear Leukocytes of Patients with Active Pulmonary Tuberculosis1 , 2006, The Journal of Immunology.

[37]  D. Guwatudde,et al.  The effect of bacille Calmette-Guérin vaccination at birth on tuberculin skin test reactivity in Ugandan children. , 1999, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.