Chemokine/cytokine production by mononuclear cells from human lymphoid tissues and their modulation by<i>Mycobacterium tuberculosis</i>antigens

Arias, Mauricio; Pantoja, Adelis E.; Jaramillo, Gabriela; López, Yurika; Mejía, Natalia; Mejía, Camila; París, Sara C.; Shattock, Robin J.; Griffin, George E.; García, Luis F.

doi:10.1111/j.1574-695x.2006.00192.x

Cited by 4 publications

(3 citation statements)

References 23 publications

(23 reference statements)

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“…The cytokine IL‐12p70 was undetectable on either testing day due probably to the inhibitory effect of IL‐10 on its production, as shown previously by Arias et al. [38].…”

Section: Discussionsupporting

confidence: 77%

Comparative Analysis of Spontaneous and Mycobacterial Antigen‐Induced Secretion of Th1, Th2 and Pro‐Inflammatory Cytokines by Peripheral Blood Mononuclear Cells of Tuberculosis Patients

2012

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The cytokines produced by T helper (Th)1 cells (IFN‐γ, IL‐2 and TNF‐β) correlate with protection, whereas the cytokines released by Th2 cells (IL‐4, IL‐5) and the anti‐inflammatory cytokine IL‐10 correlate with pathogenesis of tuberculosis (TB). However, the pro‐inflammatory cytokines (IL‐1β, IL‐6, IL‐8, TNF‐α and IL‐12p70) are responsible for both protection and pathogenesis of TB. The aim of this work was to carry out a comparative analysis of cytokines present in early (day 2) and late (day 6) cultures of peripheral blood mononuclear cells (PBMCs) obtained from pulmonary tuberculosis patients. PBMCs were cultured in vitro in the absence and presence of exogenously added complex mycobacterial antigens and RD1 peptide pool. The supernatants were collected on day 2 and day 6 of culture and assayed for secreted cytokines using the flow cytomix assay. All of the cytokines, except for IL‐12p70, were spontaneously secreted by PBMCs of 27–100% TB patients, but only TNF‐α concentration was significantly higher on day 2 than day 6 (P < 0.05). Two days following antigenic stimulation, only IL‐1β, IL‐6, TNF‐α and IL‐10 were secreted in response to some mycobacterial antigens. However, 6 days later, all of the cytokines, except for IL‐2, IL‐4, IL‐5 and IL‐8, were secreted significantly in response to all complex antigens and RD1 peptides, compared with the non‐stimulated cultures (P < 0.05). In conclusion, the study shows that the longer in vitro stimulation time (6 days) was necessary for the optimal induction of IFN‐γ and TNF‐β, and practically convenient for the detection of IL‐10, IL‐1 β, TNF‐α and IL‐6.

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“…The cytokine IL‐12p70 was undetectable on either testing day due probably to the inhibitory effect of IL‐10 on its production, as shown previously by Arias et al. [38].…”

Section: Discussionsupporting

confidence: 77%

Comparative Analysis of Spontaneous and Mycobacterial Antigen‐Induced Secretion of Th1, Th2 and Pro‐Inflammatory Cytokines by Peripheral Blood Mononuclear Cells of Tuberculosis Patients

2012

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“…Discrepancy between these results may be due to the different origin of the cells, i.e., blood monocyte-derived macrophages/DC vs PHLN, or simply that APC from PHLN respond differently to Mtb than blood-derived cells. In this regard, we reported previously that human peripheral blood MNC are more likely to be affected by the modulatory effects of Mtb Ag than cells from spleen and PHLN (43,44).…”

Section: Discussionmentioning

confidence: 91%

Mycobacterium tuberculosisAntigens Specifically Modulate CCR2 and MCP-1/CCL2 on Lymphoid Cells from Human Pulmonary Hilar Lymph Nodes

Arias

Jaramillo

López

et al. 2007

The Journal of Immunology

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Macrophages and dendritic cells are involved in the immune response to Mycobacterium tuberculosis (Mtb). Such a response, although extensively studied using animal models and cells from human blood, has not been characterized in cells from pulmonary hilar lymph nodes (PHLN). We characterized populations of myeloid APC from PHLN and determined their expression of CCR2, CCR5, CCR7, CD40, CD54, CD80, and CD86 as well as the cytokine/chemokine microenvironment before and after purified protein derivative (PPD) and mannosilated lipoarabinomannan (ManLAM) stimulation. Results show that there are at least three APC populations in PHLN, defined as CD14highHLA-DRlow/−, CD14dimHLA-DRdim, and CD14−HLA-DRhigh/dendritic cells (DC), with the largest number represented by CD14dimHLA-DRdim cells (where dim indicates intermediate levels). CD14−HLA-DRhigh/DC expressed higher levels of costimulatory molecules and lower levels of CCR2 and CCR5, but all cell populations showed similar CCR7 levels. PPD and ManLAM specifically down-regulated CCR2 expression but not that of CCR5 and CCR7, and such down-regulation was observed on all APC populations. Mtb Ag did not affect the expression of costimulatory molecules. PPD but not ManLAM specifically induced MCP-1/CCL2 production, which was likely associated with the induction of IFN-γ because this cytokine was highly induced by PPD. We characterized, for the first time, different APC from human PHLN and show that Mtb Ag exert fine and specific regulation of molecules closely associated with the immune response to Mtb infection. Because knowledge of this response in secondary lymphoid tissues is still poorly understood in humans, such studies are necessary and important for a better understanding of lymphoid cell microenvironment and migrating capacities and their role in the immunopathogenesis of tuberculosis.

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“…In addition, Mtb infection severely dysregulates immune homeostasis of the host. Mycobacterial antigens enhance cytokine and chemokine production in blood [] and elevated levels of proinflammatory cytokines in plasma are observed during pleural TB []. TB status is also reflected in the circulation by a changed transcriptional signature of blood cells suggesting altered gene expression profiles [].…”

Section: Introductionmentioning

confidence: 99%

Mycobacteria‐infected bystander macrophages trigger maturation of dendritic cells and enhance their ability to mediate HIV transinfection

et al. 2012

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Synergistic interplay between Mycobacterium tuberculosis (Mtb) and HIV in coinfected individuals leads to the acceleration of both tuberculosis and HIV disease. Mtb, as well as HIV, may modulate the function of many immune cells, including DCs. To dissect the bystander impact of Mφs infected withMtb on DC functionality, we here investigated changes in DC phenotype, cytokine profiles, and HIV-1 transinfecting ability. An in vitro system was used in which human monocyte-derived DCs were exposed to soluble factors released by Mφs infected with mycobacteria, including virulent clinical Mtb isolates and nonvirulent BCG. Soluble factors secreted from Mtb-infected Mφs, and to a lesser extent BCG-infected Mφs, resulted in the production of proinflammatory cytokines and partial upregulation of DC maturation markers. Interestingly, the HIV-1 transinfecting ability of DCs was enhanced upon exposure to soluble factors released by Mtb-infected Mφs. In summary, our study shows that DCs exposed to soluble factors released by mycobacteriainfected Mφs undergo maturation and display an augmented ability to transmit HIV-1 in trans. These findings highlight the important role of bystander effects during the course of Mtb-HIV coinfection and suggest that Mtb-infected Mφs may contribute to an environment that supports DC-mediated spread and amplification of HIV in coinfected individuals. Keywords: coinfection · dendritic cell · HIV-1 · macrophage · Mycobacterium tuberculosis Supporting Information available online IntroductionTuberculosis (TB) remains the leading cause of death among HIV-infected patients, accounting for about 26% of AIDS-related deaths [1]. Unlike other opportunistic infections affecting severely immunocompromised patients, active TB can develop throughout Correspondence: Dr. Jolanta Mazurek e-mail: Jolanta.Mazurek@ki.se the entire course of HIV infection. Pulmonary TB is often diagnosed in people with relatively intact immune systems, whereas extrapulmonary TB is seen more frequently in AIDS patients (CD4 < 200/mm 3 ) [2]. In principle, Mycobacterium tuberculosis (Mtb), which causes TB, can infect any organ in the body, but lymph nodes are the most common location for extrapulmonary TB [3]. * These authors contributed equally to this work.C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2012. 42: 1192-1202 Immunity to infection 1193The interplay between Mtb and HIV is two sided and synergistic. HIV infection contributes strongly to the reactivation of latent Mtb infection and progression to active TB. Thus, the lifetime risk of developing active TB in immunocompetent adults is estimated to be 5-10%, while this risk is increased to 5-15% annually in HIV-positive individuals [4]. In addition, Mtb infection severely dysregulates immune homeostasis of the host. Mycobacterial antigens enhance cytokine and chemokine production in blood [5] and elevated levels of proinflammatory cytokines in plasma are observed during pleural TB [6]. TB status is also reflected in the circulation by a ...

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Chemokine/cytokine production by mononuclear cells from human lymphoid tissues and their modulation byMycobacterium tuberculosisantigens

Cited by 4 publications

References 23 publications

Comparative Analysis of Spontaneous and Mycobacterial Antigen‐Induced Secretion of Th1, Th2 and Pro‐Inflammatory Cytokines by Peripheral Blood Mononuclear Cells of Tuberculosis Patients

Comparative Analysis of Spontaneous and Mycobacterial Antigen‐Induced Secretion of Th1, Th2 and Pro‐Inflammatory Cytokines by Peripheral Blood Mononuclear Cells of Tuberculosis Patients

Mycobacterium tuberculosisAntigens Specifically Modulate CCR2 and MCP-1/CCL2 on Lymphoid Cells from Human Pulmonary Hilar Lymph Nodes

Mycobacteria‐infected bystander macrophages trigger maturation of dendritic cells and enhance their ability to mediate HIV transinfection

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