Neutrophils in tuberculosis: friend or foe?

Lowe, David M.; Redford, Paul S.; Wilkinson, Robert J.; O’Garra, Anne; Martineau, Adrian R.

doi:10.1016/j.it.2011.10.003

Cited by 271 publications

(281 citation statements)

References 102 publications

(167 reference statements)

Supporting

Mentioning

265

Contrasting

Unclassified

Order By: Relevance

“…Both roles are potentially relevant in human TB where neutrophils are readily detected in the blood of patients with active TB by a signature IFN gene expression profile (Berry et al 2010), in the cerebrospinal fluid of tuberculous meningitis (Thwaites et al 2002;Lowe et al 2012) an a in pulmonary TB, where they can be abundant in both early granulomas and late cavitary granulomas (Canetti 1955;Eum et al 2010).…”

Section: Neutrophils In the Granuloma: Protective Or Pathogenic?mentioning

confidence: 99%

Immunity and Immunopathology in the Tuberculous Granuloma

Pagán

Ramakrishnan

2014

Cold Spring Harb Perspect Med

131

View full text Add to dashboard Cite

Section: Neutrophils In the Granuloma: Protective Or Pathogenic?mentioning

confidence: 99%

Immunity and Immunopathology in the Tuberculous Granuloma

Pagán

Ramakrishnan

2014

Cold Spring Harb Perspect Med

131

View full text Add to dashboard Cite

“…With regard to neutrophils, strains harboring cluster-associated mutations in Rv2813-2814c induced significantly lower ROS production and early apoptosis. Neutrophils are considered protective during early infection, when they are recruited to the site of infection, phagocytose mycobacteria (35) or mycobacteria-infected macrophages (36), and resist mycobacterial growth using ROS (36). Children with chronic granulomatous disease have a reduced oxidative burst and are more susceptible to TB (37).…”

Section: Discussionmentioning

confidence: 99%

Transmissible Mycobacterium tuberculosis Strains Share Genetic Markers and Immune Phenotypes

Nebenzahl-Guimaraes

Laarhoven²,

Mustafa

et al. 2017

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Successful transmission of tuberculosis depends on the interplay of human behavior, host immune responses, and Mycobacterium tuberculosis virulence factors. Previous studies have been focused on identifying host risk factors associated with increased transmission, but the contribution of specific genetic variations in mycobacterial strains themselves are still unknown.Objectives: To identify mycobacterial genetic markers associated with increased transmissibility and to examine whether these markers lead to altered in vitro immune responses.Methods: Using a comprehensive tuberculosis registry (n = 10,389) and strain collection in the Netherlands, we identified a set of 100 M. tuberculosis strains either least or most likely to be transmitted after controlling for host factors. We subjected these strains to wholegenome sequencing and evolutionary convergence analysis, and we repeated this analysis in an independent validation cohort. We then performed immunological experiments to measure in vitro cytokine production and neutrophil responses to a subset of the original strains with or without the identified mutations associated with increased transmissibility. Measurements and Main Results:We identified the loci espE, PE-PGRS56, Rv0197, Rv2813-2814c, and Rv2815-2816c as targets of convergent evolution among transmissible strains. We validated four of these regions in an independent set of strains, and we demonstrated that mutations in these targets affected in vitro monocyte and T-cell cytokine production, neutrophil reactive oxygen species release, and apoptosis.Conclusions: In this study, we identified genetic markers in convergent evolution of M. tuberculosis toward enhanced transmissibility in vivo that are associated with altered immune responses in vitro.

show abstract

“…Similar characteristic lesions were observed in lungs of CD4 + T celldepleted mice infected with M. tuberculosis, but not in WT mice (67). Neutrophils accumulate in situations of high pathogen load and immunological dysfunction, and they are likely to contribute to the pathology of TB (68). G-CSF, GM-CSF, IL-6, IL-8, IL-17, and other CXC chemokines recruit neutrophils to sites of infection (69).…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Matsumura

Iwai

Kato-Miyazawa

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Peroxiredoxin (PRDX)1 is an antioxidant that detoxifies hydrogen peroxide and peroxinitrite. Compared with wild-type (WT) mice, Prdx1-deficient (Prdx1−/−) mice showed increased susceptibility to Mycobacterium tuberculosis and lower levels of IFN-γ and IFN-γ–producing CD4+ T cells in the lungs after M. tuberculosis infection. IL-12 production, c-Rel induction, and p38 MAPK activation levels were lower in Prdx1−/− than in WT bone marrow–derived macrophages (BMDMs). IFN-γ–activated Prdx1−/− BMDMs did not kill M. tubercuosis effectively. NO production levels were lower, and arginase activity and arginase 1 (Arg1) expression levels were higher, in IFN-γ–activated Prdx1−/− than in WT BMDMs after M. tuberculosis infection. An arginase inhibitor, Nω-hydroxy-nor-arginine, restored antimicrobial activity and NO production in IFN-γ–activated Prdx1−/− BMDMs after M. tuberculosis infection. These results suggest that PRDX1 contributes to host defenses against M. tuberculosis. PRDX1 positively regulates IL-12 production by inducing c-Rel and activating p38 MAPK, and it positively regulates NO production by suppressing Arg1 expression in macrophages infected with M. tuberculosis.

show abstract

Neutrophils in tuberculosis: friend or foe?

Cited by 271 publications

References 102 publications

Immunity and Immunopathology in the Tuberculous Granuloma

Immunity and Immunopathology in the Tuberculous Granuloma

Transmissible Mycobacterium tuberculosis Strains Share Genetic Markers and Immune Phenotypes

Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Contact Info

Product

Resources

About