Edwin Klein
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View article: Antiretroviral treatment does not prevent extrapulmonary tuberculosis during SIV/Mtb co-infection in macaques
Antiretroviral treatment does not prevent extrapulmonary tuberculosis during SIV/Mtb co-infection in macaques Open
Co-infection with both HIV and M. tuberculosis (Mtb) results in disseminated tuberculosis (TB) and accelerated progression of HIV. Despite greater access to antiretroviral treatment (ART), it remains unclear whether suppression of HIV repl…
View article: Protection against reinfection with <i>Mycobacterium tuberculosis</i> extends across heterologous Mtb lineages
Protection against reinfection with <i>Mycobacterium tuberculosis</i> extends across heterologous Mtb lineages Open
Immunological memory elicited either through previous or ongoing M. tuberculosis (Mtb) infection provides a critical mechanism by which hosts protect against re-infection and disease progression upon Mtb re-exposure. Conversely, the uneven…
View article: Characterizing PET CT patterns and bacterial dissemination features of tuberculosis relapse in the macaque model
Characterizing PET CT patterns and bacterial dissemination features of tuberculosis relapse in the macaque model Open
Tuberculosis (TB) relapse after appropriate drug treatment is poorly understood but critical to developing shorter treatment regimens. Using a cynomolgus macaque model of human TB, macaques with active TB disease were treated with a short …
View article: Characterizing PET CT patterns and bacterial dissemination features of tuberculosis relapse in the macaque model
Characterizing PET CT patterns and bacterial dissemination features of tuberculosis relapse in the macaque model Open
Tuberculosis (TB) relapse after appropriate drug treatment is poorly understood but critical to developing shorter treatment regimens. Using a cynomolgus macaque model of human TB, macaques with active TB disease were treated with a short …
View article: The immunometabolic topography of tuberculosis granulomas governs cellular organization and bacterial control
The immunometabolic topography of tuberculosis granulomas governs cellular organization and bacterial control Open
SUMMARY Despite being heavily infiltrated by immune cells, tuberculosis (TB) granulomas often subvert the host response to Mycobacterium tuberculosis (Mtb) infection and support bacterial persistence. We previously discovered that human TB…
View article: Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes
Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes Open
Tuberculosis (TB) is a major health burden worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the BCG route and dose from 5 × 105 CFUs ID to 5 × 107 CFUs i.v. resulted in pre…
View article: CD4 T cells and CD8α+ lymphocytes are necessary for intravenous BCG-induced protection against tuberculosis in macaques
CD4 T cells and CD8α+ lymphocytes are necessary for intravenous BCG-induced protection against tuberculosis in macaques Open
Tuberculosis (TB) is a major cause of morbidity and mortality worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the route and dose of BCG vaccination from 5ξ10 5 CFU ID to 5…
View article: CD4<sup>+</sup>T cells are homeostatic regulators during<i>Mtb</i>reinfection
CD4<sup>+</sup>T cells are homeostatic regulators during<i>Mtb</i>reinfection Open
Immunological priming – either in the context of prior infection or vaccination – elicits protective responses against subsequent Mycobacterium tuberculosis ( Mtb ) infection. However, the changes that occur in the lung cellular milieu pos…
View article: CD8+ lymphocytes are critical for early control of tuberculosis in macaques
CD8+ lymphocytes are critical for early control of tuberculosis in macaques Open
The functional role of CD8+ lymphocytes in tuberculosis remains poorly understood. We depleted innate and/or adaptive CD8+ lymphocytes in macaques and showed that loss of all CD8α+ cells (using anti-CD8α antibody) significantly impaired ea…
View article: Characterizing the Spectrum of Latent<i>Mycobacterium tuberculosis</i>in the Cynomolgus Macaque Model: Clinical, Immunologic, and Imaging Features of Evolution
Characterizing the Spectrum of Latent<i>Mycobacterium tuberculosis</i>in the Cynomolgus Macaque Model: Clinical, Immunologic, and Imaging Features of Evolution Open
Mycobacterium tuberculosis infection outcomes have been described as active tuberculosis or latent infection but a spectrum of outcomes is now recognized. We used a nonhuman primate model, which recapitulates human infection, to characteri…
View article: T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques
T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques Open
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understanding host…
View article: Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control
Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control Open
Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of …
View article: T cell transcription factor expression evolves as adaptive immunity matures in granulomas from<i>Mycobacterium tuberculosis</i>-infected cynomolgus macaques
T cell transcription factor expression evolves as adaptive immunity matures in granulomas from<i>Mycobacterium tuberculosis</i>-infected cynomolgus macaques Open
SUMMARY Mycobacterium tuberculosis ( Mtb) , the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understa…
View article: SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and shedding of infectious virus from both respiratory and gastrointestinal tracts
SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and shedding of infectious virus from both respiratory and gastrointestinal tracts Open
Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green…
View article: Lymph nodes—The neglected battlefield in tuberculosis
Lymph nodes—The neglected battlefield in tuberculosis Open
Lymph nodes, particularly thoracic lymph nodes, are among the most common sites of extrapulmonary tuberculosis (TB). However, Mycobacterium tuberculosis (Mtb) infection in these organs is understudied. Aside from being sites of initiation …
View article: Interleukin-18 and cytotoxic impairment are independent and synergistic causes of murine virus-induced hyperinflammation
Interleukin-18 and cytotoxic impairment are independent and synergistic causes of murine virus-induced hyperinflammation Open
Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperinflammatory syndromes typically associated with underlying hematologic and rheumatic diseases, respectively. Familial HLH is assoc…
View article: SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts
SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts Open
Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green…
View article: Evaluation of IL-1 Blockade as an Adjunct to Linezolid Therapy for Tuberculosis in Mice and Macaques
Evaluation of IL-1 Blockade as an Adjunct to Linezolid Therapy for Tuberculosis in Mice and Macaques Open
In 2017 over 550,000 estimated new cases of multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) occurred, emphasizing a need for new treatment strategies. Linezolid (LZD) is a potent antibiotic for drug-resistant Gram-positive infecti…
View article: Prevention of tuberculosis in macaques after intravenous BCG immunization
Prevention of tuberculosis in macaques after intravenous BCG immunization Open
Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide 1 . The only available vaccine, BCG (Bacillus Calmette–Guérin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the ma…
View article: IL-10 Impairs Local Immune Response in Lung Granulomas and Lymph Nodes during Early <i>Mycobacterium tuberculosis</i> Infection
IL-10 Impairs Local Immune Response in Lung Granulomas and Lymph Nodes during Early <i>Mycobacterium tuberculosis</i> Infection Open
Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a major global health problem. Lung granulomas are organized structures of host immune cells that function to contain the bacteria. Cytokine expression is a critical …
View article: <i>Clostridium difficile</i> Enterocolitis in a Captive Geoffroy’s Spider Monkey (<i>Ateles geoffroyi</i>) and Common Marmosets (<i>Callithrix jacchus</i>)
<i>Clostridium difficile</i> Enterocolitis in a Captive Geoffroy’s Spider Monkey (<i>Ateles geoffroyi</i>) and Common Marmosets (<i>Callithrix jacchus</i>) Open
Clostridium difficile is a well-documented cause of enterocolitis in several species, including humans, with limited documentation in New World nonhuman primates. We report several cases of C. difficile–associated pseudomembranous enteroco…