Tags

Type your tag names separated by a space and hit enter

Lactic acid bacteria enhance autophagic ability of mononuclear phagocytes by increasing Th1 autophagy-promoting cytokine (IFN-gamma) and nitric oxide (NO) levels and reducing Th2 autophagy-restraining cytokines (IL-4 and IL-13) in response to Mycobacterium tuberculosis antigen.
Int Immunopharmacol. 2010 Jun; 10(6):694-706.II

Abstract

BACKGROUND AND OBJECTIVES

Control of the intracellular Mycobacterium tuberculosis (Mtb), mainly requires an appropriate ratio of Th1/Th2 cytokines to induce autophagy, a physiologically, and immunologically regulated process that has recently been highlighted as an innate defense mechanism against intracellular pathogens. Current vaccines/adjuvants induce both protective Th1 autophagy-promoting cytokines, such as IFN-gamma, and immunosuppressive Th2 autophagy-restraining cytokines, such as IL-4 and IL-13. TB infection itself is also characterized by relatively high levels of Th2 cytokines, which down-regulate Th1 responses and subsequently subvert adequate protective immunity, and a low ratio of IFN-gamma/IL-4. Therefore, there is a need for a safe and non-toxic vaccine/adjuvant that will induce Th1 autophagy-promoting cytokine (IFN-gamma) secretion and suppress the pre-existing subversive Th2 autophagy-restraining cytokines (IL-4 and IL-13). As lactic acid bacteria (LAB) belonging to the natural intestinal microflora and their components have been shown to shift immune responses against other antigens from Th2-type cytokines toward Th1-type cytokines like IFN-gamma, we investigated whether LAB can improve the polarization of Th1/Th2 cytokines and autophagic ability of mononuclear phagocytes in response to Mtb antigen.

METHODS

Peripheral blood mononuclear cells (PBMCs), which are a part of the mononuclear phagocyte system and source of crucial macrophage activators in the in vivo situation, and human monocyte-derived macrophages (HMDMs) were treated with Mtb antigen in the presence or absence of two strains of LAB, L. rhammosus GG (LGG) and Bifidobacterium bifidum MF 20/5 (B.b). PBMCs cell culture supernatants were analyzed for the production of the autophagy-promoting factors IFN-gamma, and nitric oxide (NO) and the autophagy-restraining cytokines IL-4 and IL-13, using ELISA and Griess assays to detect the production of cytokines and NO, respectively. In HMDMs, expression of microtubule-associated protein 1 light chain 3 (LC3-I), membrane-associated (LC3-II) forms of LC3 protein and Beclin-1, as hallmarks of autophagy, were assessed using Western blot to detect the autophagy markers. The secreted interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin (IL)-12 and transformig growth factor-beta (TGF-beta), and chemokine (C-C motif) ligand 18 (CCL18) from HMDMs were determined by ELISA. Also, reverse transcription polymerase chain reaction (RT-PCR) analysis was used to assess the mRNA expressions of CCL18 in HMDMs.

RESULTS

Treatment of PBMCs with either Mtb antigen or with LAB significantly increased the IFN-gamma and NO production. Combination of Mtb antigen and LAB led to synergistic increase in IFN-gamma, and an additive increase in NO. Treatment with Mtb antigen alone significantly increased the IL-4 and IL-13 production. LAB significantly decreased IL-4 and IL-13 secretion in both unstimulated and Mtb antigen-stimulated PBMCs. The IFN-gamma/IL-4+IL-13 ratio was enhanced, indicating Th1/Th2 polarization. Treatment of macrophages with combined use of Mtb antigen and LAB led to an additive increase in Beclin-1, LC3-II expression, as well as in synergistic increase in IL-12 production. Treatment of macrophages with combined use of Mtb antigen and LAB led to a decrease in IL-6, IL-10, and CCL18 secretion. LAB inhibited the secretion of TGF-beta by Mtb-stimulated macrophages, however not significantly. Treatment of macrophages with combined use of Mtb antigen and LAB led to a decrease in CCL18 mRNA expression.

CONCLUSION

Our study implies that LAB may reinforce the response of the mononuclear phagocytes to Mtb antigen by inducing production of the autophagy-promoting factors IFN-gamma and NO, while decreasing the Th2 autophagy-restraining cytokines IL-4 and IL-13. Hence, combination of Mtb antigen and LAB may perhaps be safer in more efficacious TB vaccine formulation.

Authors+Show Affiliations

Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Hermann-Weigmann-Str 1, D-24103 Kiel, Germany. ghadimi@bafm.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20381647

Citation

Ghadimi, Darab, et al. "Lactic Acid Bacteria Enhance Autophagic Ability of Mononuclear Phagocytes By Increasing Th1 Autophagy-promoting Cytokine (IFN-gamma) and Nitric Oxide (NO) Levels and Reducing Th2 Autophagy-restraining Cytokines (IL-4 and IL-13) in Response to Mycobacterium Tuberculosis Antigen." International Immunopharmacology, vol. 10, no. 6, 2010, pp. 694-706.
Ghadimi D, de Vrese M, Heller KJ, et al. Lactic acid bacteria enhance autophagic ability of mononuclear phagocytes by increasing Th1 autophagy-promoting cytokine (IFN-gamma) and nitric oxide (NO) levels and reducing Th2 autophagy-restraining cytokines (IL-4 and IL-13) in response to Mycobacterium tuberculosis antigen. Int Immunopharmacol. 2010;10(6):694-706.
Ghadimi, D., de Vrese, M., Heller, K. J., & Schrezenmeir, J. (2010). Lactic acid bacteria enhance autophagic ability of mononuclear phagocytes by increasing Th1 autophagy-promoting cytokine (IFN-gamma) and nitric oxide (NO) levels and reducing Th2 autophagy-restraining cytokines (IL-4 and IL-13) in response to Mycobacterium tuberculosis antigen. International Immunopharmacology, 10(6), 694-706. https://doi.org/10.1016/j.intimp.2010.03.014
Ghadimi D, et al. Lactic Acid Bacteria Enhance Autophagic Ability of Mononuclear Phagocytes By Increasing Th1 Autophagy-promoting Cytokine (IFN-gamma) and Nitric Oxide (NO) Levels and Reducing Th2 Autophagy-restraining Cytokines (IL-4 and IL-13) in Response to Mycobacterium Tuberculosis Antigen. Int Immunopharmacol. 2010;10(6):694-706. PubMed PMID: 20381647.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lactic acid bacteria enhance autophagic ability of mononuclear phagocytes by increasing Th1 autophagy-promoting cytokine (IFN-gamma) and nitric oxide (NO) levels and reducing Th2 autophagy-restraining cytokines (IL-4 and IL-13) in response to Mycobacterium tuberculosis antigen. AU - Ghadimi,Darab, AU - de Vrese,Michael, AU - Heller,Knut J, AU - Schrezenmeir,Juergen, Y1 - 2010/04/07/ PY - 2010/01/20/received PY - 2010/03/08/revised PY - 2010/03/30/accepted PY - 2010/4/13/entrez PY - 2010/4/13/pubmed PY - 2010/9/4/medline SP - 694 EP - 706 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 10 IS - 6 N2 - BACKGROUND AND OBJECTIVES: Control of the intracellular Mycobacterium tuberculosis (Mtb), mainly requires an appropriate ratio of Th1/Th2 cytokines to induce autophagy, a physiologically, and immunologically regulated process that has recently been highlighted as an innate defense mechanism against intracellular pathogens. Current vaccines/adjuvants induce both protective Th1 autophagy-promoting cytokines, such as IFN-gamma, and immunosuppressive Th2 autophagy-restraining cytokines, such as IL-4 and IL-13. TB infection itself is also characterized by relatively high levels of Th2 cytokines, which down-regulate Th1 responses and subsequently subvert adequate protective immunity, and a low ratio of IFN-gamma/IL-4. Therefore, there is a need for a safe and non-toxic vaccine/adjuvant that will induce Th1 autophagy-promoting cytokine (IFN-gamma) secretion and suppress the pre-existing subversive Th2 autophagy-restraining cytokines (IL-4 and IL-13). As lactic acid bacteria (LAB) belonging to the natural intestinal microflora and their components have been shown to shift immune responses against other antigens from Th2-type cytokines toward Th1-type cytokines like IFN-gamma, we investigated whether LAB can improve the polarization of Th1/Th2 cytokines and autophagic ability of mononuclear phagocytes in response to Mtb antigen. METHODS: Peripheral blood mononuclear cells (PBMCs), which are a part of the mononuclear phagocyte system and source of crucial macrophage activators in the in vivo situation, and human monocyte-derived macrophages (HMDMs) were treated with Mtb antigen in the presence or absence of two strains of LAB, L. rhammosus GG (LGG) and Bifidobacterium bifidum MF 20/5 (B.b). PBMCs cell culture supernatants were analyzed for the production of the autophagy-promoting factors IFN-gamma, and nitric oxide (NO) and the autophagy-restraining cytokines IL-4 and IL-13, using ELISA and Griess assays to detect the production of cytokines and NO, respectively. In HMDMs, expression of microtubule-associated protein 1 light chain 3 (LC3-I), membrane-associated (LC3-II) forms of LC3 protein and Beclin-1, as hallmarks of autophagy, were assessed using Western blot to detect the autophagy markers. The secreted interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin (IL)-12 and transformig growth factor-beta (TGF-beta), and chemokine (C-C motif) ligand 18 (CCL18) from HMDMs were determined by ELISA. Also, reverse transcription polymerase chain reaction (RT-PCR) analysis was used to assess the mRNA expressions of CCL18 in HMDMs. RESULTS: Treatment of PBMCs with either Mtb antigen or with LAB significantly increased the IFN-gamma and NO production. Combination of Mtb antigen and LAB led to synergistic increase in IFN-gamma, and an additive increase in NO. Treatment with Mtb antigen alone significantly increased the IL-4 and IL-13 production. LAB significantly decreased IL-4 and IL-13 secretion in both unstimulated and Mtb antigen-stimulated PBMCs. The IFN-gamma/IL-4+IL-13 ratio was enhanced, indicating Th1/Th2 polarization. Treatment of macrophages with combined use of Mtb antigen and LAB led to an additive increase in Beclin-1, LC3-II expression, as well as in synergistic increase in IL-12 production. Treatment of macrophages with combined use of Mtb antigen and LAB led to a decrease in IL-6, IL-10, and CCL18 secretion. LAB inhibited the secretion of TGF-beta by Mtb-stimulated macrophages, however not significantly. Treatment of macrophages with combined use of Mtb antigen and LAB led to a decrease in CCL18 mRNA expression. CONCLUSION: Our study implies that LAB may reinforce the response of the mononuclear phagocytes to Mtb antigen by inducing production of the autophagy-promoting factors IFN-gamma and NO, while decreasing the Th2 autophagy-restraining cytokines IL-4 and IL-13. Hence, combination of Mtb antigen and LAB may perhaps be safer in more efficacious TB vaccine formulation. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/20381647/Lactic_acid_bacteria_enhance_autophagic_ability_of_mononuclear_phagocytes_by_increasing_Th1_autophagy_promoting_cytokine__IFN_gamma__and_nitric_oxide__NO__levels_and_reducing_Th2_autophagy_restraining_cytokines__IL_4_and_IL_13__in_response_to_Mycobacterium_tuberculosis_antigen_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(10)00098-6 DB - PRIME DP - Unbound Medicine ER -