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Article ; Online: A protocol to analyze single-cell RNA-seq data from Mycobacterium tuberculosis-infected mice lung.

Akter, Sadia / Khader, Shabaana A

STAR protocols

2023 Volume 4, Issue 3, Page(s) 102544

Abstract: Processing and analyzing single-cell RNA-seq (scRNA-seq) from lung cells are challenging due to the complexity of cell subtypes and biological variations within sample groups. Here, we present a protocol for performing an in-depth assessment on lung ... ...

Abstract	Processing and analyzing single-cell RNA-seq (scRNA-seq) from lung cells are challenging due to the complexity of cell subtypes and biological variations within sample groups. Here, we present a protocol for performing an in-depth assessment on lung lymphocyte populations derived from healthy and Mycobacterium tuberculosis-infected mice. We describe steps for downloading processed scRNA-seq data, integrating samples across different conditions, and performing cluster analysis. We then detail procedures for identifying lymphoid cell subtypes, differential analysis, and pathway enrichment analysis. For complete details on the use and execution of this protocol, please refer to Akter et al. (2022).
MeSH term(s)	Animals ; Mice ; Mycobacterium tuberculosis/genetics ; Single-Cell Gene Expression Analysis ; Cluster Analysis
Language	English
Publishing date	2023-08-31
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102544
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Article ; Online: Rifampicin drug resistance and host immunity in tuberculosis: more than meets the eye.

Bobba, Suhas / Khader, Shabaana A

Trends in immunology

2023 Volume 44, Issue 9, Page(s) 712–723

Abstract: Tuberculosis (TB) is the leading cause of death due to an infectious agent, with more than 1.5 million deaths attributed to TB annually worldwide. The global dissemination of drug resistance across Mycobacterium tuberculosis (Mtb) strains, causative of ... ...

Abstract	Tuberculosis (TB) is the leading cause of death due to an infectious agent, with more than 1.5 million deaths attributed to TB annually worldwide. The global dissemination of drug resistance across Mycobacterium tuberculosis (Mtb) strains, causative of TB, resulted in an estimated 450 000 cases of drug-resistant (DR) TB in 2021. Dysregulated immune responses have been observed in patients with multidrug resistant (MDR) TB, but the effects of drug resistance acquisition and impact on host immunity remain obscure. In this review, we compile studies that span aspects of altered host-pathogen interactions and highlight research that explores how drug resistance and immunity might intersect. Understanding the immune processes differentially induced during DR TB would aid the development of rational therapeutics and vaccines for patients with MDR TB.
MeSH term(s)	Humans ; Rifampin ; Antitubercular Agents/pharmacology ; Antitubercular Agents/therapeutic use ; Tuberculosis/drug therapy ; Mycobacterium tuberculosis ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/microbiology
Chemical Substances	Rifampin (VJT6J7R4TR) ; Antitubercular Agents
Language	English
Publishing date	2023-08-03
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2023.07.003
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Zs.A 1601: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Inflammatory comorbidities: to train or not to train?

Bobba, Suhas / Khader, Shabaana A

Trends in immunology

2022 Volume 43, Issue 6, Page(s) 420–422

Abstract: Inflammatory stimuli reprogram innate immune cells to generate rigorous responses to future challenge with heterologous stimuli through trained immunity. Li et al. show that training of hematopoietic stem cells (HSCs) in the bone marrow primes cells to ... ...

Abstract	Inflammatory stimuli reprogram innate immune cells to generate rigorous responses to future challenge with heterologous stimuli through trained immunity. Li et al. show that training of hematopoietic stem cells (HSCs) in the bone marrow primes cells to generate more inflammatory myeloid progeny and, thereby, mechanistically links inflammatory comorbidities.
MeSH term(s)	Bone Marrow ; Hematopoietic Stem Cells ; Humans ; Immunity, Innate
Language	English
Publishing date	2022-05-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2022.04.005
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Zs.A 1601: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Saponin TQL1055 adjuvant-containing vaccine confers protection upon

Ahmed, Mushtaq / Farris, Eric / Swanson, Rosemary V / Das, Shibali / Yang, Yan / Martin, Tyler / Khader, Shabaana A

Human vaccines & immunotherapeutics

2024 Volume 20, Issue 1, Page(s) 2302070

Abstract: Tuberculosis (TB), caused by the intracellular ... ...

Abstract	Tuberculosis (TB), caused by the intracellular pathogen
MeSH term(s)	Adult ; Child ; Infant ; Humans ; Animals ; Mice ; Child, Preschool ; Mycobacterium tuberculosis ; BCG Vaccine ; Adjuvants, Immunologic ; Tuberculosis Vaccines ; Tuberculosis, Pulmonary/prevention & control ; Mycobacterium bovis ; Saponins
Chemical Substances	BCG Vaccine ; Adjuvants, Immunologic ; Tuberculosis Vaccines ; Saponins
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.1080/21645515.2024.2302070
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Zs.A 6967: Show issues

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Article ; Online: Elevated Level of Circulating but Not Urine S100A8/A9 Identifies Poor COVID-19 Outcomes.

Mellett, Leah / Amarasinghe, Gaya / Farnsworth, Christopher W / Khader, Shabaana A

ACS infectious diseases

2023 Volume 9, Issue 10, Page(s) 1815–1820

Abstract: The alarmin calprotectin (S100A8/A9) is thought to drive a cytokine storm, a hallmark of severe COVID-19. Recent studies report circulating S100A8/A9 levels can distinguish COVID-19 severity but have only been conducted in non-U.S. cohorts and mainly ... ...

Abstract	The alarmin calprotectin (S100A8/A9) is thought to drive a cytokine storm, a hallmark of severe COVID-19. Recent studies report circulating S100A8/A9 levels can distinguish COVID-19 severity but have only been conducted in non-U.S. cohorts and mainly focus on serum S100A8/A9 levels. Thus, we quantified S100A8/A9 in serum and urine samples from a hospital cohort in St. Louis, Missouri, to expand the understanding of S100A8/A9 as a prognostic biomarker for COVID-19. Elevated S100A8/A9 serum levels were observed in ICU patients (
MeSH term(s)	Humans ; Calgranulin B ; COVID-19/diagnosis ; Calgranulin A ; Leukocyte L1 Antigen Complex ; Biomarkers
Chemical Substances	Calgranulin B ; Calgranulin A ; Leukocyte L1 Antigen Complex ; Biomarkers
Language	English
Publishing date	2023-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.3c00249
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Article ; Online: S100A8/A9 in COVID-19 pathogenesis: Impact on clinical outcomes.

Mellett, Leah / Khader, Shabaana A

Cytokine & growth factor reviews

2021 Volume 63, Page(s) 90–97

Abstract: Coronavirus disease 2019 (COVID-19) has a broad range of clinical manifestations, highlighting the need for specific diagnostic tools to predict disease severity and improve patient prognosis. Recently, calprotectin (S100A8/A9) has been proposed as a ... ...

Abstract	Coronavirus disease 2019 (COVID-19) has a broad range of clinical manifestations, highlighting the need for specific diagnostic tools to predict disease severity and improve patient prognosis. Recently, calprotectin (S100A8/A9) has been proposed as a potential biomarker for COVID-19, as elevated serum S100A8/A9 levels are associated with critical COVID-19 cases and can distinguish between mild and severe disease states. S100A8/A9 is an alarmin that mediates host proinflammatory responses during infection and it has been postulated that S100A8/A9 modulates the cytokine storm; the hallmark of fatal COVID-19 cases. However, it has yet to be determined if S100A8/A9 is a bona-fide biomarker for COVID-19. S100A8/A9 is widely implicated in a variety of inflammatory conditions, such as cystic fibrosis (CF) and chronic obstructive pulmonary disorder (COPD), as well as pulmonary infectious diseases, including tuberculosis and influenza. Therefore, understanding how S100A8/A9 levels correlate with immune responses during inflammatory diseases is necessary to evaluate its candidacy as a potential COVID-19 biomarker. This review will outline the protective and detrimental roles of S100A8/A9 during infection, summarize the recent findings detailing the contributions of S100A8/A9 to COVID-19 pathogenesis, and highlight its potential as diagnostic biomarker and a therapeutic target for pulmonary infectious diseases, including COVID-19.
MeSH term(s)	Biomarkers ; COVID-19 ; Calgranulin A ; Calgranulin B ; Humans ; SARS-CoV-2
Chemical Substances	Biomarkers ; Calgranulin A ; Calgranulin B ; S100A8 protein, human ; S100A9 protein, human
Language	English
Publishing date	2021-10-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1330534-7
ISSN	1879-0305 ; 1359-6101
ISSN (online)	1879-0305
ISSN	1359-6101
DOI	10.1016/j.cytogfr.2021.10.004
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Zs.A 2653: Show issues

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Article ; Online: Lung type 3 innate lymphoid cells respond early following

Das, Shibali / Chauhan, Kuldeep Singh / Ahmed, Mushtaq / Akter, Sadia / Lu, Lan / Colonna, Marco / Khader, Shabaana A

mBio

2024 Volume 15, Issue 4, Page(s) e0329923

Abstract: Tuberculosis is the leading cause of death due to an infectious disease worldwide. Innate lymphoid type 3 cells (ILC3s) mediate early protection during : Importance: Tuberculosis is a leading cause of death due to a single infectious agent accounting ... ...

Abstract	Tuberculosis is the leading cause of death due to an infectious disease worldwide. Innate lymphoid type 3 cells (ILC3s) mediate early protection during Importance: Tuberculosis is a leading cause of death due to a single infectious agent accounting for 1.6 million deaths each year. In our study, we determined the role of type 3 innate lymphoid cells in early immune events necessary for achieving protection during
MeSH term(s)	Mice ; Animals ; Immunity, Innate ; Lymphocytes ; Tuberculosis ; Lung ; Mycobacterium tuberculosis ; Vaccines
Chemical Substances	Vaccines
Language	English
Publishing date	2024-02-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.03299-23
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Article ; Online: The Tale of IL-12 and IL-23: A Paradigm Shift.

Khader, Shabaana A / Thirunavukkarasu, Shyamala

Journal of immunology (Baltimore, Md. : 1950)

2019 Volume 202, Issue 3, Page(s) 629–630

MeSH term(s)	Animals ; Autoimmune Diseases/immunology ; Humans ; Inflammation/immunology ; Interleukin-12/immunology ; Interleukin-23/immunology ; Mice
Chemical Substances	Interleukin-23 ; Interleukin-12 (187348-17-0)
Language	English
Publishing date	2019-01-22
Publishing country	United States
Document type	Classical Article ; Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1801603
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Article ; Online: Immunometabolism during Mycobacterium tuberculosis Infection.

Howard, Nicole C / Khader, Shabaana A

Trends in microbiology

2020 Volume 28, Issue 10, Page(s) 832–850

Abstract: Over a quarter of the world's population is infected with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Approximately 3.4% of new and 18% of recurrent cases of TB are multidrug-resistant (MDR) or rifampicin-resistant. Recent ...

Abstract	Over a quarter of the world's population is infected with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Approximately 3.4% of new and 18% of recurrent cases of TB are multidrug-resistant (MDR) or rifampicin-resistant. Recent evidence has shown that certain drug-resistant strains of Mtb modulate host metabolic reprogramming, and therefore immune responses, during infection. However, it remains unclear how widespread these mechanisms are among circulating MDR Mtb strains and what impact drug-resistance-conferring mutations have on immunometabolism during TB. While few studies have directly addressed metabolic reprogramming in the context of drug-resistant Mtb infection, previous literature examining how drug-resistance mutations alter Mtb physiology and differences in the immune response to drug-resistant Mtb provides significant insights into how drug-resistant strains of Mtb differentially impact immunometabolism.
MeSH term(s)	Animals ; Antitubercular Agents/pharmacology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Humans ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/metabolism ; Rifampin/pharmacology ; Tuberculosis/immunology ; Tuberculosis/microbiology
Chemical Substances	Antitubercular Agents ; Bacterial Proteins ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2020-05-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2020.04.010
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Zs.A 3738: Show issues

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Article ; Online: A protective role for type I interferon signaling following infection with Mycobacterium tuberculosis carrying the rifampicin drug resistance-conferring RpoB mutation H445Y.

Bobba, Suhas / Chauhan, Kuldeep S / Akter, Sadia / Das, Shibali / Mittal, Ekansh / Mathema, Barun / Philips, Jennifer A / Khader, Shabaana A

PLoS pathogens

2024 Volume 20, Issue 4, Page(s) e1012137

Abstract: Interleukin-1 (IL-1) signaling is essential for controlling virulent Mycobacterium tuberculosis (Mtb) infection since antagonism of this pathway leads to exacerbated pathology and increased susceptibility. In contrast, the triggering of type I interferon ...

Abstract	Interleukin-1 (IL-1) signaling is essential for controlling virulent Mycobacterium tuberculosis (Mtb) infection since antagonism of this pathway leads to exacerbated pathology and increased susceptibility. In contrast, the triggering of type I interferon (IFN) signaling is associated with the progression of tuberculosis (TB) disease and linked with negative regulation of IL-1 signaling. However, mice lacking IL-1 signaling can control Mtb infection if infected with an Mtb strain carrying the rifampin-resistance conferring mutation H445Y in its RNA polymerase β subunit (rpoB-H445Y Mtb). The mechanisms that govern protection in the absence of IL-1 signaling during rpoB-H445Y Mtb infection are unknown. In this study, we show that in the absence of IL-1 signaling, type I IFN signaling controls rpoB-H445Y Mtb replication, lung pathology, and excessive myeloid cell infiltration. Additionally, type I IFN is produced predominantly by monocytes and recruited macrophages and acts on LysM-expressing cells to drive protection through nitric oxide (NO) production to restrict intracellular rpoB-H445Y Mtb. These findings reveal an unexpected protective role for type I IFN signaling in compensating for deficiencies in IL-1 pathways during rpoB-H445Y Mtb infection.
MeSH term(s)	Mycobacterium tuberculosis ; Interferon Type I/metabolism ; Animals ; Mice ; Rifampin/pharmacology ; Signal Transduction ; DNA-Directed RNA Polymerases/metabolism ; DNA-Directed RNA Polymerases/genetics ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Mutation ; Mice, Inbred C57BL ; Drug Resistance, Bacterial/genetics ; Tuberculosis/microbiology ; Tuberculosis/immunology ; Tuberculosis/genetics ; Mice, Knockout
Chemical Substances	Interferon Type I ; Rifampin (VJT6J7R4TR) ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; Bacterial Proteins ; rpoB protein, Mycobacterium tuberculosis
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1012137
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