Increased Lytic Efficiency of Bovine Macrophages Trained with Killed Mycobacteria

Abstract

Innate immunity is evolutionarily conserved in multicellular organisms and was considered to lack memory until very recently. One of its more characteristic mechanisms is phagocytosis, the ability of cells to engulf, process and eventually destroy any injuring agent. We report the results of an ex vivo experiment in bovine macrophages in which improved clearance of Mycobacterium bovis (M. bovis) was induced by pre-exposure to a heat killed M. bovis preparation. The effects were independent of humoral and cellular adaptive immune responses and lasted up to six months. Specifically, our results demonstrate the existence of a training effect in the lytic phase of phagocytosis that can be activated by killed mycobacteria, thus suggesting a new mechanism of vaccine protection. These findings are compatible with the recently proposed concept of trained immunity, which was developed to explain the observation that innate immune responses provide unspecific protection against pathogens including other than those that originally triggered the immune response.

Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates

“…bovis specific antigenic stimulation after vaccination is generally accepted to play an important role in the protective mechanism against BTB, emphasizing the role of cell-mediated immunity. This role was confirmed in an ‘ex vivo’ experiment carried out by Juste et al [ 19 ] which determined that bovine macrophages trained with the heat-killed M . bovis vaccine through intramuscular injection exhibited an increased lytic capacity, which was furthermore proposed as an underlying mechanism of vaccine protection.…”

“…avium ; 1000 IU/ml) and PPD-F (purified protein derivative of M . fortuitum ; 28.5 μg/ml, ARC-Onderstepoort Veterinary Institute) [ 19 ]. One aliquot of whole blood was left unstimulated to serve as a negative control.…”

“…Vaccination with formalin-inactivated BCG in a Novasome™ adjuvant conferred protection against tuberculosis in guinea pigs [ 13 ] and subsequent evaluation in cattle by Whelan et al [ 16 ] demonstrated strong IFN-γ and IgG responses. Promising results of parenteral and oral vaccination with a heat-killed Mycobacterium bovis vaccine have since been obtained in several species [ 17 – 19 ]. The aim of the present study was to compare the immune response profiles in response to the parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle.…”

Training of Primary Chicken Monocytes Results in Enhanced Pro-Inflammatory Responses

“…NO production of trained monocytes may lead to increased killing capacity upon phagocytosis [26]. Indeed, a study in bovine monocyte-derived macrophages showed that increased bacterial killing capacity could be induced by macrophage training upon stimulation with heat-killed Mycobacteria bovis in vivo [27]. In that study, this was referred to as innate immune training.…”

Hypothesis: stimulation of trained immunity as adjunctive immunotherapy in cancer

“…TI results in enhanced cytokine production upon stimulation of myeloid and NK cells with nonrelated micro-organisms, as well as an increased phagocytosis and killing of pathogens [50,69] Induction of TI in myeloid cells seems also to have important adjuvant effects on lymphocyte activation, as a randomized trial of BCG as a booster for influenza vaccination has demonstrated improved lymphocyte responses [70]. These initial data provide arguments that TI may also improve antitumor lymphocyte responses and may be beneficial as adjuvant therapy in malignancies.…”