Subcutaneous Bacillus Calmette-Guérin Administration Induces Innate Training in Monocytes in Preweaned Holstein Calves

Overview

Journal Immunohorizons

Specialty Allergy & Immunology

Date 2023 Sep 22

PMID 37737907

Authors

Beulah E R Samuel

Teresia W Maina

Jodi L McGill

Affiliations

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Abstract

The bacillus Calmette-Guérin (BCG) vaccine, administered to prevent tuberculosis, is a well-studied inducer of trained immunity in human and mouse monocytes. We have previously demonstrated that aerosol BCG administration induces innate training in calves. The current study aimed to determine whether s.c. BCG administration could induce innate training, identify the cell type involved, and determine whether innate training promoted resistance to bovine respiratory syncytial virus (BRSV) infection, a major cause of bovine respiratory disease in preweaned calves. A total of 24 calves were enrolled at 1-3 d of age and blocked by age into two treatment groups (BCG, n = 12; control, n = 12). BCG was given s.c. to preweaned calves. The control calves received PBS. We observed a trained phenotype, demonstrated by enhanced cytokine production in response to in vitro stimulation with LPS (TLR-4 agonist) in PBMCs and CD14+ monocytes from the BCG group 2 wk (IL-1β, p = 0.002) and 4 wk (IL-1β, p = 0.005; IL-6, p = 0.013) after BCG administration, respectively. Calves were experimentally infected via aerosol inoculation with BRSV strain 375 at 5 wk after BCG administration and necropsied on day 8 postinfection. There were no differences in disease manifestation between the treatment groups. Restimulation of bronchoalveolar lavage fluid cells isolated on day 8 after BRSV infection revealed enhanced IL-1β (p = 0.014) and IL-6 (p = 0.010) production by the BCG group compared with controls. In conclusion, results from our study show that s.c. administration of the BCG vaccine can induce trained immunity in bovine monocytes and influence cytokine production in the lung environment after BRSV infection.

Citing Articles

Evidence of innate training in bovine γδ T cells following subcutaneous BCG administration.

Samuel B, Diaz F, Maina T, Corbett R, Tuggle C, McGill J Front Immunol. 2024; 15:1423843.

PMID: 39100669 PMC: 11295143. DOI: 10.3389/fimmu.2024.1423843.

References

Moorlag S, Khan N, Novakovic B, Kaufmann E, Jansen T, van Crevel R . β-Glucan Induces Protective Trained Immunity against Mycobacterium tuberculosis Infection: A Key Role for IL-1. Cell Rep. 2020; 31(7):107634. PMC: 7242907. DOI: 10.1016/j.celrep.2020.107634. View

Kleinnijenhuis J, Quintin J, Preijers F, Joosten L, Jacobs C, Xavier R . BCG-induced trained immunity in NK cells: Role for non-specific protection to infection. Clin Immunol. 2014; 155(2):213-9. PMC: 5084088. DOI: 10.1016/j.clim.2014.10.005. View

Moorlag S, Rodriguez-Rosales Y, Gillard J, Fanucchi S, Theunissen K, Novakovic B . BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils. Cell Rep. 2020; 33(7):108387. PMC: 7672522. DOI: 10.1016/j.celrep.2020.108387. View

Jarvi N, Balu-Iyer S . Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins. BioDrugs. 2021; 35(2):125-146. PMC: 7848667. DOI: 10.1007/s40259-020-00465-4. View

Bekkering S, Quintin J, Joosten L, van der Meer J, Netea M, Riksen N . Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arterioscler Thromb Vasc Biol. 2014; 34(8):1731-8. DOI: 10.1161/ATVBAHA.114.303887. View

Kleinnijenhuis J, Quintin J, Preijers F, Benn C, Joosten L, Jacobs C . Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J Innate Immun. 2013; 6(2):152-8. PMC: 3944069. DOI: 10.1159/000355628. View

Byrne K, Loving C, McGill J . Innate Immunomodulation in Food Animals: Evidence for Trained Immunity?. Front Immunol. 2020; 11:1099. PMC: 7291600. DOI: 10.3389/fimmu.2020.01099. View

Diaz F, Guerra-Maupome M, McDonald P, Rivera-Perez D, Kalergis A, McGill J . A Recombinant BCG Vaccine Is Safe and Immunogenic in Neonatal Calves and Reduces the Clinical Disease Caused by the Respiratory Syncytial Virus. Front Immunol. 2021; 12:664212. PMC: 8108697. DOI: 10.3389/fimmu.2021.664212. View

Sacco R, Nonnecke B, Palmer M, Waters W, Lippolis J, Reinhardt T . Differential expression of cytokines in response to respiratory syncytial virus infection of calves with high or low circulating 25-hydroxyvitamin D3. PLoS One. 2012; 7(3):e33074. PMC: 3297628. DOI: 10.1371/journal.pone.0033074. View

10.

Lajqi T, Braun M, Alexander Kranig S, Frommhold D, Poschl J, Hudalla H . LPS Induces Opposing Memory-like Inflammatory Responses in Mouse Bone Marrow Neutrophils. Int J Mol Sci. 2021; 22(18). PMC: 8469609. DOI: 10.3390/ijms22189803. View

11.

Takahashi Y, Morales Valencia M, Yu Y, Ouchi Y, Takahashi K, Shokhirev M . Transgenerational inheritance of acquired epigenetic signatures at CpG islands in mice. Cell. 2023; 186(4):715-731.e19. DOI: 10.1016/j.cell.2022.12.047. View

12.

Kleinnijenhuis J, Quintin J, Preijers F, Joosten L, Ifrim D, Saeed S . Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012; 109(43):17537-42. PMC: 3491454. DOI: 10.1073/pnas.1202870109. View

13.

Verma D, Parasa V, Raffetseder J, Martis M, Mehta R, Netea M . Anti-mycobacterial activity correlates with altered DNA methylation pattern in immune cells from BCG-vaccinated subjects. Sci Rep. 2017; 7(1):12305. PMC: 5615063. DOI: 10.1038/s41598-017-12110-2. View

14.

Bekkering S, Blok B, Joosten L, Riksen N, van Crevel R, Netea M . In Vitro Experimental Model of Trained Innate Immunity in Human Primary Monocytes. Clin Vaccine Immunol. 2016; 23(12):926-933. PMC: 5139603. DOI: 10.1128/CVI.00349-16. View

15.

Hilligan K, Namasivayam S, Clancy C, OMard D, Oland S, Robertson S . Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge. J Exp Med. 2021; 219(2). PMC: 8669500. DOI: 10.1084/jem.20211862. View

16.

Stensballe L, Nante E, Jensen I, Kofoed P, Poulsen A, Jensen H . Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: a beneficial effect of BCG vaccination for girls community based case-control study. Vaccine. 2005; 23(10):1251-7. DOI: 10.1016/j.vaccine.2004.09.006. View

17.

Garly M, Martins C, Bale C, Balde M, Hedegaard K, Gustafson P . BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?. Vaccine. 2003; 21(21-22):2782-90. DOI: 10.1016/s0264-410x(03)00181-6. View

18.

Mahmoud A, Slate J, Hong S, Yoon I, McGill J . Supplementing a Saccharomyces cerevisiae fermentation product modulates innate immune function and ameliorates bovine respiratory syncytial virus infection in neonatal calves. J Anim Sci. 2020; 98(8). PMC: 7457959. DOI: 10.1093/jas/skaa252. View

19.

Arts R, Moorlag S, Novakovic B, Li Y, Wang S, Oosting M . BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell Host Microbe. 2018; 23(1):89-100.e5. DOI: 10.1016/j.chom.2017.12.010. View

20.

Kaufmann E, Khan N, Tran K, Ulndreaj A, Pernet E, Fontes G . BCG vaccination provides protection against IAV but not SARS-CoV-2. Cell Rep. 2022; 38(10):110502. PMC: 8858710. DOI: 10.1016/j.celrep.2022.110502. View