Emergence of Polyfunctional Cytotoxic CD4+ T Cells in Mycobacterium avium Immune Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected Patients

Hsu, Denise C.; Breglio, Kimberly F.; Pei, Luxin; Wong, Chun-Shu; Andrade, Bruno B.; Sheikh, Virginia; Smelkinson, Margery; Petrovas, Constantinos; Rupert, Adam; Gil-Santana, Leonardo; Zelazny, Adrian M.; Holland, Steven M.; Olivier, Kenneth N.; Barber, Daniel L.; Sereti, Irini

doi:10.1093/cid/ciy016

Cited by 31 publications

(29 citation statements)

References 46 publications

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“…Immune cells polyfunctionality, in terms of cytokine production, has been recently described in lymphocytes 44 and monocytes 10 , in the context of infectious diseases. In sterile inflammatory conditions such as SCA, the polyfunctionality still remains to be evaluated.…”

Section: Discussionmentioning

confidence: 99%

Hydroxyurea alters circulating monocyte subsets and dampens its inflammatory potential in sickle cell anemia patients

Guarda

Silveira-Mattos

Yahouédéhou

et al. 2019

Sci Rep

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Sickle cell anemia (SCA) is a hemolytic disease in which vaso-occlusion is an important pathophysiological mechanism. The treatment is based on hydroxyurea (HU), which decreases leukocyte counts and increases fetal hemoglobin synthesis. Different cell types are thought to contribute to vaso-occlusion. Nevertheless, the role of monocytes subsets remains unclear. We investigated frequencies of monocytes subsets in blood and their response to HU therapy, testing their ability to express pro-inflammatory molecules and tissue factor (TF). We identified major changes in monocyte subsets, with classical monocytes (CD14++CD16−) appearing highly frequent in who were not taking HU, whereas those with patrolling phenotype (CD14dimCD16+) were enriched in individuals undergoing therapy. Additionally, HU decreased the production of TNF-α, IL1-β, IL-6, IL-8 as well as TF by the LPS-activated monocytes. Likewise, frequency of TF-expressing monocytes is increased in patients with previous vaso-occlusion. Moreover, activated monocytes expressing TF produced several pro-inflammatory cytokines simultaneously. Such polyfunctional capacity was dramatically dampened by HU therapy. The frequency of classical monocytes subset was positively correlated with percentage cytokine producing cells upon LPS stimulation. These findings suggest that classical monocytes are the subset responsible for multiple pro-inflammatory cytokine production and possibly drive inflammation and vaso-occlusion in SCA which is damped by HU.

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Section: Discussionmentioning

confidence: 99%

Hydroxyurea alters circulating monocyte subsets and dampens its inflammatory potential in sickle cell anemia patients

Guarda

Silveira-Mattos

Yahouédéhou

et al. 2019

Sci Rep

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“…Genetic susceptibility to disseminated mycobacterial infection is well described and should be considered in anyone who presents with disseminated disease without HIV infection (Wu and Holland, 2015). Even diseases that are often diagnosed in childhood can present with disseminated infection in adulthood when their mutation results in a less severe phenotype (Hsu et al, 2018). Host control depends on the interleukin 12-interferon pathway that connects myeloid and lymphoid cells.…”

Section: Discussionmentioning

confidence: 99%

Host Variability in NTM Disease: Implications for Research Needs

2018

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Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that may cause opportunistic infections in susceptible hosts. Lung infections in immunocompetent persons with structural lung disease are most common, while disseminated disease occurs primarily in immunocompromised individuals. Human disease caused by certain species, such as Mycobacterium avium complex, Mycobacterium abscessus, and Mycobacterium kansasii, is increasing in incidence and varies by geographic distribution. The spectrum of NTM disease varies widely in presentation and clinical outcome, but certain patterns can be organized into clinical phenotypes. Treatment options are limited, lengthy, and often toxic. The purpose of this case-based review is to provide non-clinician scientists with a better understanding of human NTM disease with an aim to stimulate more research and development.

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“…We have previously shown that using analysis of Spearman correlation matrices can provide insights on the degree and quality of inflammation in TB-HIV as well as in other diseases [26][27][28]. The results obtained from the canonical correlation model described above indicated that there were differences in the correlation profiles between the inflammatory markers from PTB vs. EPTB patients and we next utilized Circos plots to visualize such distinctions.…”

Section: Unique Correlation Profiles Of Inflammatory Biomarkers In Pementioning

confidence: 96%

“…Baseline and post treatment plasma samples originated from persons with signs and symptoms indicative of active TB and who were HIV-uninfected and who were not undertaking antitubercular therapy or healthy controls that were enrolled into a prospective clinical protocol to assess response to chemotherapy (NCT01071603) conducted at the Henan Chest Hospital (HCH) in Zhengzhou, China from 2010 to 2012, as described previously [6,15,16]. Individuals with pulmonary tuberculosis (PTB) were similar to those presenting with extra pulmonary tuberculosis (EPTB) with regard to age (median [IQR] in years: 27 [23-44.7] vs. 27 [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36], respectively; P = 0.1933; Supplemental Table 1) and gender (P = 0.4916, Table S1), with higher frequency of male individuals (61.7% vs. 52% vs. respectively).…”

Section: Characteristics Of the Study Participantsmentioning

confidence: 99%

Changes in inflammatory protein and lipid mediator profiles persist after antitubercular treatment of pulmonary and extrapulmonary tuberculosis: A prospective cohort study

et al. 2019

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Background: The identification of meaningful biomarkers of tuberculosis (TB) has potential to improve diagnosis, disease staging and prediction of treatment outcomes. It has been shown that active pulmonary TB (PTB) is associated with qualitative and quantitative changes in systemic immune profile, suggesting a chronic inflammatory imbalance. Here we characterized the profile of PTB and extrapulmonary TB (EPTB) in a prospective cohort study. Methods: We measured a panel of 27 inflammatory cytokines, soluble receptors, and lipid mediators in peripheral blood from patients with PTB or EPTB from a prospective clinical study in China. Multidimensional analyses were performed to describe associations between plasma levels of biomarkers and different TB disease presentation profiles. Results: Mycobacterium tuberculosis infection induced changes in both the expression and correlation profiles of plasma mediators of inflammation in patients with PTB compared to those with EPTB. Increases in mycobacterial loads in sputum smears were associated with rises in concentrations of several molecules involved in TB pathogenesis, such as IL-1β, IFN-α, IL-10 and PGF2α. Moreover, PTB patients presenting with severe disease exhibited a distinct inflammatory profile hallmarked by heightened levels of TNF-α, IL-1β, IL17, IL-18 and IL-27. Interestingly, while antitubercular treatment (ATT) resulted in early changes of plasma concentrations of markers in PTB, changes were delayed in EPTB patients. Exploratory analyses of the molecular degree of perturbation (MDP) of the inflammatory mediators before and during ATT suggested the occurrence of infection

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Emergence of Polyfunctional Cytotoxic CD4+ T Cells in Mycobacterium avium Immune Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected Patients

Cited by 31 publications

References 46 publications

Hydroxyurea alters circulating monocyte subsets and dampens its inflammatory potential in sickle cell anemia patients

Hydroxyurea alters circulating monocyte subsets and dampens its inflammatory potential in sickle cell anemia patients

Host Variability in NTM Disease: Implications for Research Needs

Changes in inflammatory protein and lipid mediator profiles persist after antitubercular treatment of pulmonary and extrapulmonary tuberculosis: A prospective cohort study

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