• 1.

    Babu S, Nutman TB , 2014. Immunology of lymphatic filariasis. Parasite Immunol 36: 338346.

  • 2.

    Semnani RT , 2013. The interaction between filarial parasites and human monocyte/macrophage populations. Adv Exp Med Biol 785: 4956.

    • Search Google Scholar
    • Export Citation
  • 3.

    Semnani RT et al.2006. Filaria-induced monocyte dysfunction and its reversal following treatment. Infect Immun 74: 44094417.

  • 4.

    Babu S, Kumaraswami V, Nutman TB , 2009. Alternatively activated and immunoregulatory monocytes in human filarial infections. J Infect Dis 199: 18271837.

    • Search Google Scholar
    • Export Citation
  • 5.

    Narasimhan PB, Bennuru S, Meng Z, Cotton RN, Elliott KR, Ganesan S, McDonald-Fleming R, Veenstra TD, Nutman TB, Tolouei Semnani R , 2016. Microfilariae of Brugia malayi inhibit the mTOR pathway and induce autophagy in human dendritic cells. Infect Immun 84: 24632472.

    • Search Google Scholar
    • Export Citation
  • 6.

    Mehrpour M, Esclatine A, Beau I, Codogno P , 2010. Overview of macroautophagy regulation in mammalian cells. Cell Res 20: 748762.

  • 7.

    Levine B, Mizushima N, Virgin HW , 2011. Autophagy in immunity and inflammation. Nature 469: 323335.

  • 8.

    Wang Y et al.2017. Brucella dysregulates monocytes and inhibits macrophage polarization through LC3-dependent autophagy. Front Immunol 8: 691.

    • Search Google Scholar
    • Export Citation
  • 9.

    Kumar P , 2017. IFNγ-producing CD4 T lymphocytes: the double-edged swords in tuberculosis. Clin Transl Med 6: 21.

  • 10.

    Rovetta AI et al.2014. IFNG-mediated immune responses enhance autophagy against Mycobacterium tuberculosis antigens in patients with active tuberculosis. Autophagy 10: 21092121.

    • Search Google Scholar
    • Export Citation
  • 11.

    Babu S, Ganley LM, Klei TR, Shultz LD, Rajan TV , 2000. Role of gamma interferon and interleukin-4 in host defense against the human filarial parasite Brugia malayi. Infect Immun 68: 30343035.

    • Search Google Scholar
    • Export Citation
  • 12.

    Ghadimi D, de Vrese M, Heller KJ, 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. Int Immunopharmacol 10: 694706.

    • Search Google Scholar
    • Export Citation
  • 13.

    Acovic A, Gazdic M, Jovicic N, Harrell CR, Fellabaum C, Arsenijevic N, Volarevic V , 2018. Role of indoleamine 2,3-dioxygenase in pathology of the gastrointestinal tract. Therap Adv Gastroenterol 11: 1756284818815334.

    • Search Google Scholar
    • Export Citation
  • 14.

    Zhang Y, Morgan MJ, Chen K, Choksi S, Liu ZG , 2012. Induction of autophagy is essential for monocyte-macrophage differentiation. Blood 119: 28952905.

    • Search Google Scholar
    • Export Citation
  • 15.

    Liu K, Zhao E, Ilyas G, Lalazar G, Lin Y, Haseeb M, Tanaka KE, Czaja MJ , 2015. Impaired macrophage autophagy increases the immune response in obese mice by promoting proinflammatory macrophage polarization. Autophagy 11: 271284.

    • Search Google Scholar
    • Export Citation
  • 16.

    Yong S, Lau S , 1979. Rapid separation of tryptophan, kynurenines, and indoles using reversed-phase high-performance liquid chromatography. J Chromatogr A 175: 343346.

    • Search Google Scholar
    • Export Citation
  • 17.

    Braun D, Longman RS, Albert ML , 2005. A two-step induction of indoleamine 2,3-dioxygenase (IDO) activity during dendritic-cell maturation. Blood 106: 23752381.

    • Search Google Scholar
    • Export Citation
  • 18.

    McEwan DG , 2017. Host–pathogen interactions and subversion of autophagy. Essays Biochem 61: 687697.

  • 19.

    Su CW, Cao Y, Zhang M, Kaplan J, Su L, Fu Y, Walker WA, Xavier R, Cherayil BJ, Shi HN , 2012. Helminth infection impairs autophagy-mediated killing of bacterial enteropathogens by macrophages. J Immunol 189: 14591466.

    • Search Google Scholar
    • Export Citation
  • 20.

    Matsuzawa T, Kim BH, Shenoy AR, Kamitani S, Miyake M, Macmicking JD , 2012. IFN-γ elicits macrophage autophagy via the p38 MAPK signaling pathway. J Immunol 189: 813818.

    • Search Google Scholar
    • Export Citation
  • 21.

    Chang Y-P et al.2010. Autophagy facilitates IFN-γ-induced Jak2-STAT1 activation and cellular Inflammation. J Biol Chem 285: 2871528722.

  • 22.

    Fougeray S, Mami I, Bertho G, Beaune P, Thervet E, Pallet N , 2012. Tryptophan depletion and the kinase GCN2 mediate IFN-γ-induced autophagy. J Immunol 189: 29542964.

    • Search Google Scholar
    • Export Citation
  • 23.

    Donovan MJ, Tripathi V, Favila MA, Geraci NS, Lange MC, Ballhorn W, McDowell MA , 2012. Indoleamine 2,3-dioxygenase (IDO) induced by Leishmania infection of human dendritic cells. Parasite Immunol 34: 464472.

    • Search Google Scholar
    • Export Citation
  • 24.

    Jürgens B, Hainz U, Fuchs D, Felzmann T, Heitger A , 2009. Interferon-gamma-triggered indoleamine 2,3-dioxygenase competence in human monocyte-derived dendritic cells induces regulatory activity in allogeneic T cells. Blood 114: 32353243.

    • Search Google Scholar
    • Export Citation
  • 25.

    Wolf B, Posnick D, Fisher JL, Lewis LD, Ernstoff MS , 2009. Indoleamine-2,3-dioxygenase enzyme expression and activity in polarized dendritic cells. Cytotherapy 11: 10841089.

    • Search Google Scholar
    • Export Citation
  • 26.

    Carlin JM, Borden EC, Sondel PM, Byrne GI , 1989. Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes. J Leukoc Biol 45: 2934.

    • Search Google Scholar
    • Export Citation
  • 27.

    MacKenzie CR, González RG, Kniep E, Roch S, Däubener W , 1999. Cytokine mediated regulation of interferon-gamma-induced IDO activation. Adv Exp Med Biol 467: 533539.

    • Search Google Scholar
    • Export Citation
  • 28.

    Saito K, Suyama K, Nishida K, Sei Y, Basile AS , 1996. Early increases in TNF-α, IL-6 and IL-1β levels following transient cerebral ischemia in gerbil brain. Neurosci Lett 206: 149152.

    • Search Google Scholar
    • Export Citation
  • 29.

    Fujigaki S, Saito K, Sekikawa K, Tone S, Takikawa O, Fujii H, Wada H, Noma A, Seishima M , 2001. Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-gamma-independent mechanism. Eur J Immunol 31: 23132318.

    • Search Google Scholar
    • Export Citation
  • 30.

    Sasisekhar B, Aparna M, Augustin DJ, Kaliraj P, Kar SK, Nutman TB, Narayanan RB , 2005. Diminished monocyte function in microfilaremic patients with lymphatic filariasis and its relationship to altered lymphoproliferative responses. Infect Immun 73: 33853393.

    • Search Google Scholar
    • Export Citation
  • 31.

    Semnani RT, Mahapatra L, Moore V, Sanprasert V, Nutman TB, 2011. Functional and phenotypic characteristics of alternative activation induced in human monocytes by interleukin-4 or the parasitic nematode Brugia malayi. Infect Immun 79: 3957–3965.

  • 32.

    Semnani RT, Liu AY, Sabzevari H, Kubofcik J, Zhou J, Gilden JK, Nutman TB , 2003. Brugia malayi microfilariae induce cell death in human dendritic cells, inhibit their ability to make IL-12 and IL-10, and reduce their capacity to activate CD4+ T cells. J Immunol 171: 19501960.

    • Search Google Scholar
    • Export Citation
  • 33.

    Chun Y, Kim J , 2018. Autophagy: an essential degradation program for cellular homeostasis and life. Cells 7: 278.

  • 34.

    Deretic V, Levine B , 2009. Autophagy, immunity, and microbial adaptations. Cell Host Microbe 5: 527549.

  • 35.

    Cyrino LT, Araújo AP, Joazeiro PP, Vicente CP, Giorgio S, 2012. In vivo and in vitro Leishmania amazonensis infection induces autophagy in macrophages. Tissue Cell 44: 401408.

    • Search Google Scholar
    • Export Citation
  • 36.

    Ricciardi et al., 2021. Extracellular vesicles released from the filarial parasite Brugia malayi downregulate the host mTOR pathway. PLoS Negl Trop Dis 15: e0008884.

  • 37.

    Eason RJ, Bell KS, Marshall FA, Rodgers DT, Pineda MA, Steiger CN, Al-Riyami L, Harnett W, Harnett MM , 2016. The helminth product, ES-62 modulates dendritic cell responses by inducing the selective autophagolysosomal degradation of TLR-transducers, as exemplified by PKCδ. Sci Rep 6: 37276.

    • Search Google Scholar
    • Export Citation
  • 38.

    Saitoh T, Akira S, 2010. Regulation of innate immune responses by autophagy-related proteins. J Cell Biol 189: 925935

  • 39.

    Siqueira M da S, Ribeiro R de M, Travassos LH , 2018. Autophagy and its interaction with intracellular bacterial pathogens. Front Immunol 9: 935.

    • Search Google Scholar
    • Export Citation
  • 40.

    Shibutani ST, Saitoh T, Nowag H, Münz C, Yoshimori T , 2015. Autophagy and autophagy-related proteins in the immune system. Nat Immunol 16: 10141024.

    • Search Google Scholar
    • Export Citation
  • 41.

    Chen P, Cescon M, Bonaldo P , 2014. Autophagy-mediated regulation of macrophages and its applications for cancer. Autophagy 10: 192200.

  • 42.

    Zhong Z, Sanchez-Lopez E, Karin M , 2016. Autophagy, inflammation, and immunity: a troika governing cancer and its treatment. Cell 166: 288298.

    • Search Google Scholar
    • Export Citation
  • 43.

    Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ , 2009. CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 284: 3434234354.

    • Search Google Scholar
    • Export Citation
  • 44.

    Chang CP, Su YC, Hu CW, Lei HY , 2013. TLR2-dependent selective autophagy regulates NF-κB lysosomal degradation in hepatoma-derived M2 macrophage differentiation. Cell Death Differ 20: 515523.

    • Search Google Scholar
    • Export Citation
  • 45.

    Yang M, Liu J, Shao J, Qin Y, Ji Q, Zhang X, Du J , 2014. Cathepsin S-mediated autophagic flux in tumor-associated macrophages accelerate tumor development by promoting M2 polarization. Mol Cancer 13: 43.

    • Search Google Scholar
    • Export Citation
  • 46.

    Lee DE, Bareja A, Bartlett DB, White JP , 2019. Autophagy as a therapeutic target to enhance aged muscle regeneration. Cells 8: 183.

  • 47.

    Yamaguchi R, Kawata J, Yamamoto T, Ishimaru Y, Sakamoto A, Ono T, Narahara S, Sugiuchi H, Hirose E, Yamaguchi Y , 2015. Mechanism of interferon-gamma production by monocytes stimulated with myeloperoxidase and neutrophil extracellular traps. Blood Cells Mol Dis 55: 127133.

    • Search Google Scholar
    • Export Citation
  • 48.

    Kraaij MD, Vereyken EJF, Leenen PJM, van den Bosch TPP, Rezaee F, Betjes MGH, Baan CC, Rowshani AT , 2014. Human monocytes produce interferon-gamma upon stimulation with LPS. Cytokine 67: 712.

    • Search Google Scholar
    • Export Citation
  • 49.

    Rajan TV, Porte P, Yates JA, Keefer L, Shultz LD , 1996. Role of nitric oxide in host defense against an extracellular, metazoan parasite, Brugia malayi. Infect Immun 64: 33513353.

    • Search Google Scholar
    • Export Citation
  • 50.

    Verma SK, Joseph SK, Verma R, Kushwaha V, Parmar N, Yadav PK, Thota JR, Kar S, Murthy PK , 2015. Protection against filarial infection by 45–49 kDa molecules of Brugia malayi via IFN-γ-mediated iNOS induction. Vaccine 33: 527534.

    • Search Google Scholar
    • Export Citation
  • 51.

    Taylor MJ, Cross HF, Mohammed AA, Trees AJ, Bianco AE , 1996. Susceptibility of Brugia malayi and Onchocerca lienalis microfilariae to nitric oxide and hydrogen peroxide in cell-free culture and from IFN gamma-activated macrophages. Parasitology 112: 315322.

    • Search Google Scholar
    • Export Citation
  • 52.

    Rodrigues AA et al.2012. IFN-γ plays a unique role in protection against low virulent Trypanosoma cruzi strain. PLoS Negl Trop Dis 6: e1598.

    • Search Google Scholar
    • Export Citation
  • 53.

    Mbongue JC, Nicholas DA, Torrez TW, Kim NS, Firek AF, Langridge WHR , 2015. The role of indoleamine 2,3-dioxygenase in immune suppression and autoimmunity. Vaccines (Basel) 3: 703729.

    • Search Google Scholar
    • Export Citation
  • 54.

    Xiao C, Chen Y, Liang X, Xie Z, Zhang M, Li R, Li Z, Fu X, Yu X, Shi W , 2014. A modified HPLC method improves the simultaneous determination of plasma kynurenine and tryptophan concentrations in patients following maintenance hemodialysis. Exp Ther Med 7: 907910.

    • Search Google Scholar
    • Export Citation
  • 55.

    Mellor AL, Lemos H, Huang L , 2017. Indoleamine 2,3-dioxygenase and tolerance: where are we now? Front Immunol 8: 1360.

  • 56.

    Andersen MH , 2012. The specific targeting of immune regulation: T-cell responses against Indoleamine 2,3-dioxygenase. Cancer Immunol Immunother 61: 12891297.

    • Search Google Scholar
    • Export Citation
  • 57.

    Knubel CP, Martínez FF, Fretes RE, Díaz Lujan C, Theumer MG, Cervi L, Motrán CC , 2010. Indoleamine 2,3-dioxigenase (IDO) is critical for host resistance against Trypanosoma cruzi. FASEB J 24: 26892701.

    • Search Google Scholar
    • Export Citation
  • 58.

    Rani R, Jordan MB, Divanovic S, Herbert DR , 2012. IFN-γ–driven IDO production from macrophages protects IL-4Rα–deficient mice against lethality during Schistosoma mansoni infection. Am J Pathol 180: 20012008.

    • Search Google Scholar
    • Export Citation
  • 59.

    Jo EK, Yuk JM, Shin DM, Sasakawa C , 2013. Roles of autophagy in elimination of intracellular bacterial pathogens. Front Immunol 4: 97.

  • 60.

    Kalvakolanu DV, Gade P, 2012. IFNG and autophagy. A critical role for the ER-stress mediator ATF6 in controlling bacterial infections. Autophagy 8: 16731674.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 1389 1389 129
Full Text Views 23 23 2
PDF Downloads 33 33 3
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Brugia malayi Microfilariae Induce Autophagy through an Interferon-γ Dependent Mechanism in Human Monocytes

View More View Less
  • 1 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;
  • | 2 Microscopy Unit, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Bethesda, Maryland
Restricted access

ABSTRACT.

Monocyte dysfunction in helminth infection is one of the mechanisms proposed to explain the diminished parasite antigen-specific T cell responses seen with patent filarial infection. In fact, monocytes from filariae-infected individuals demonstrate internalized filarial antigens and, as a consequence, express inhibitory surface molecules and have diminished cytokine production. To investigate the mechanisms underlying monocyte dysfunction in filarial infections, purified human monocytes were exposed to live microfilariae (mf) of Brugia malayi, and the mRNA and protein expression of important inhibitory and/or autophagy-related molecules were assessed. Our data indicate that mf-induced autophagy in human monocytes shown by the formation of autophagic vesicles, by the upregulation in the mRNA expression of autophagy-related genes BCN1, LC3B, ATG5, ATG7 (P < 0.05), and by increase in the levels of LC3B protein. Furthermore, this mf-induced autophagy increased the levels of monocyte CD206 expression. In addition, mf significantly induced the frequency of interferon (IFN)-γ+ human monocytes and at the same time induced the mRNA expression of indoleamine 2,3-dioxygenase (IDO) through an IFN-γ-dependent mechanism; significantly enhanced tryptophan degradation (an indicator of IDO activity; P < 0.005). Interestingly, this autophagy induction by mf in monocytes was IFN-γ-dependent but IDO-independent as was reversed by anti-IFN-γ but not by an IDO inhibitor. Our data collectively suggest that mf of Brugia malayi regulate the function of monocytes by induction of IDO and IFN-γ, induce autophagy through an IFN-γ-dependent mechanism, and increase M2 phenotype through induction of autophagy; all acting in concert to drive monocyte dysfunction.

Author Notes

Address correspondence to Roshanak Tolouei Semnani, Autoimmunity and Translational Immunology, Precigen, Inc., 20358 Seneca Meadows Pkwy, Germantown, MD 20876. E-mail: rsemnani@precigen.com

Authors’ addresses: Prakash Babu Narasimhan, Department of Clinical Immunology, SSB, JIPMER, Puducherry, India, E-mail: nprakbab@gmail.com. Sameha Tariq, Leor Akabas, and Thomas B. Nutman, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, E-mails: sameha-tarig@gmail.com, leor.akabas@gmail.com, and tnutman@niaid.nih.gov. Roshanak Tolouei Semani, Precigen, Inc., Germantown, MD, E-mail: rsemnani@precigen.com. David W. Dorward, Microscopy Unit, Research Technologies Branch. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Bethesda, MD, E-mail: ddorward@outlook.com.

Save