T cell responses to DosR and Rpf proteins in actively and latently infected individuals from Colombia

Riaño, Felipe; Arroyo, Leonar; París, Sara C.; Rojas, Mauricio; Friggen, Annemieke H.; Meijgaarden, Krista E. van; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.; García, Luis F.; Barrera, Luis F.

doi:10.1016/j.tube.2011.12.005

Cited by 53 publications

(50 citation statements)

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“…Although LTBi tend to show a high proportion of CD4 ϩ IFN-␥ ϩ T cells compared to that in ATB, our results and those of others did not show significant differences in the frequency of IFN-␥-producing cells between them (60,68). Our group, however, using PBMC cultures supplemented with autologous serum and after in vitro restimulation at 120 h of culture, has previously reported a lower frequency of IFN-␥-producing cells in ATB than in LTBi after stimulation with specific mycobacterial antigens or PPD (55,57). The clinical heterogeneity of ATB as shown by the AFB sputum results ranging from 1ϩ to 3ϩ may explain the high variability found in the specific response to CFP-10 and PPD in this group.…”

Section: Discussionsupporting

confidence: 44%

Reduced Frequency of Memory T Cells and Increased Th17 Responses in Patients with Active Tuberculosis

Marín

París

Rojas

et al. 2012

Clin. Vaccine Immunol.

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Section: Discussionsupporting

confidence: 44%

Reduced Frequency of Memory T Cells and Increased Th17 Responses in Patients with Active Tuberculosis

Marín

París

Rojas

et al. 2012

Clin. Vaccine Immunol.

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“…Various human cohort studies showed preferential recognition of DosRencoded proteins, in particular Rv1733c, Rv2029c, Rv2627c, and Rv2628, by T cells from individuals with LTBI and to a lesser extent by TB patients (6)(7)(8)(9). Also, latency antigens can induce CD4 ϩ and CD8 ϩ T cells in TST-converted individuals who were infected with M. tuberculosis decades ago in the preantibiotic era and yet never developed TB (10,11).…”

mentioning

confidence: 99%

Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

Coppola

Eeden

Wilson

et al. 2015

Clin Vaccine Immunol

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Despite the availability of a vaccine and chemotherapeutic agents, tuberculosis (TB) remains the second leading cause of death from an infectious disease worldwide, annually causing around 9 million new cases and almost 2 million deaths (1). The highest burdens are found in low-income regions: Africa harbors about 25% of the world's TB cases and more than half have been counted in Asia (1). Furthermore, surveys with tuberculin skin tests (TST) suggest that one-third of the world's population is latently infected with Mycobacterium tuberculosis, which constitutes a huge reservoir with a 3 to 10% lifetime risk of developing TB (1, 2).It has long been recognized that the efficacy of vaccination with Mycobacterium bovis BCG, still the only registered TB vaccine, can be enhanced by a booster or replacement vaccine protecting against reactivating TB from latency (3). M. tuberculosis latency antigens (Ags), encoded by the DosR regulon, are upregulated in vitro under conditions that tubercle bacilli are thought to encounter in vivo during persistence in immunocompetent hosts (4) and in mouse models for latent M. tuberculosis infection (LTBI) (5). This discovery caused a change in focus in the search for a novel antigen(s) able to enhance long-term vaccine efficacy. Various human cohort studies showed preferential recognition of DosRencoded proteins, in particular Rv1733c, Rv2029c, Rv2627c, and Rv2628, by T cells from individuals with LTBI and to a lesser extent by TB patients (6-9). Also, latency antigens can induce CD4 ϩ and CD8 ϩ T cells in TST-converted individuals who were infected with M. tuberculosis decades ago in the preantibiotic era and yet never developed TB (10, 11).In mouse models using chronic, low-dose M. tuberculosis infection mimicking human LTBI, the preferential recognition of the DosR regulon in latent infection was further established (5) and provided evidence that BCG fails to induce a significant response to latency antigens despite their presence in the BCG genome. Also, a triple fusion protein, designated H56, including the latency/starvation antigen Rv2660 coupled to the early-stage proteins Ag85B and ESAT-6, provided protection by both pre-and postinfection vaccination in nonhuman primates (12,13). A similar improvement in long-term protection against M. tuberculosis was observed in mice after intradermal inoculation of recombinant BCG expressing the latency-associated antigens Rv2659c, Rv3407, and Rv1733c (14).Synthetic long peptides (SLPs), administered with adjuvants, are proven efficient vaccines for tumor therapy (15)(16)(17)(18)(19). Despite the success of this vaccine strategy, SLPs have not yet been applied to design new TB vaccines. Recognition of cognate antigen presented by either T cells or B cells will lead to an abortive proliferative response and death of the responding T cells.The immunogenicity of Rv1733c, which was the most commonly recognized latency antigen in M. tuberculosis-exposed household contacts from South Africa, Gambia, and Uganda (9), as well as the improved long...

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“…Studies have confirmed that Rpf are immunogenic in humans generating significant immune responses in both patients with active and latent disease (Chegou et al, 2012;Kassa et al, 2012;Riano et al, 2012). All Rpf proteins appear to be immunogenic with significant Tcell responses demonstrable in LTBI patients using interferon gamma release assays (IGRAs) (Commandeur et al, 2011;Geluk et al, 2014;Huang et al, 2013;Riano et al, 2012;Schuck et al, 2009).…”

Section: Rpf Expression In Human Infectionmentioning

confidence: 92%

“…All Rpf proteins appear to be immunogenic with significant Tcell responses demonstrable in LTBI patients using interferon gamma release assays (IGRAs) (Commandeur et al, 2011;Geluk et al, 2014;Huang et al, 2013;Riano et al, 2012;Schuck et al, 2009). Whether immune responses to Rpf are protective or not is unclear.…”

Section: Rpf Expression In Human Infectionmentioning

confidence: 99%

“…In a study of long term latently infected patients who did not develop tuberculosis, significant single and double cytokine producing CD4 þ and CD8 þ T-cells specific to RpfA were detected (Commandeur et al, 2011). Two studies showed that in patients with pulmonary tuberculosis, RpfA, B, D&E induced a significantly lower proportion of IFNc producing CD4 þ T-cells compared to those with LTBI (Riano et al, 2012;Schuck et al, 2009). Collectively this indirect evidence suggests that responses directed to Rpf antigens may strengthen immune surveillance in LTBI and prevent reactivation.…”

Section: Rpf Expression In Human Infectionmentioning

confidence: 99%

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Resuscitation-promoting factors are important determinants of the pathophysiology inMycobacterium tuberculosisinfection

Rosser

Stover

Pareek

et al. 2017

Critical Reviews in Microbiology

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Resuscitation promoting factors (Rpf) are peptidoglycan-hydrolyzing enzymes that are pivotal in the resuscitation of quiescent actinobacteria including Mycobacterium tuberculosis. From the published data, it is clear that Rpf are required for the resuscitation of non-replicating bacilli and pathogenesis in murine infection model of tuberculosis, although their direct influence on human Mycobacterium tuberculosis infection is ill-defined. In this review, we describe the progress in the understanding of the roles that Rpf play in human tuberculosis pathogenesis and importance of bacilli dependent upon Rpf for growth for the outcome of human tuberculosis. We outline how this research is opening up important opportunities for the diagnosis, treatment and prevention of human disease, progress in which is essential to attain the ultimate goal of tuberculosis eradication.ARTICLE HISTORY

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T cell responses to DosR and Rpf proteins in actively and latently infected individuals from Colombia

Cited by 53 publications

References 53 publications

Reduced Frequency of Memory T Cells and Increased Th17 Responses in Patients with Active Tuberculosis

Reduced Frequency of Memory T Cells and Increased Th17 Responses in Patients with Active Tuberculosis

Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

Resuscitation-promoting factors are important determinants of the pathophysiology inMycobacterium tuberculosisinfection

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