Immune Evasion of Mycoplasma bovis

Abstract

Mycoplasma bovis (M. bovis) causes various chronic inflammatory diseases, including mastitis and bronchopneumonia, in dairy and feed cattle. It has been found to suppress the host immune response during infection, leading to the development of chronic conditions. Both in vitro and in vivo studies have confirmed that M. bovis can induce proinflammatory cytokines and chemokines in the host. This consists of an inflammatory response in the host that causes pathological immune damage, which is essential for the pathogenic mechanism of M. bovis. Additionally, M. bovis can escape host immune system elimination and, thus, cause chronic infection. This is accomplished by preventing phagocytosis and inhibiting key responses, including the neutrophil respiratory burst and the development of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) that lead to the creation of an extracellular bactericidal network, in addition to inhibiting monocyte and alveolar macrophage apoptosis and inducing monocytes to produce anti-inflammatory factors, thus inducing the apoptosis of peripheral blood mononuclear cells (PBMCs), inhibiting their proliferative response and resulting in their invasion. Together, these conditions lead to long-term M. bovis infection. In terms of the pathogenic mechanism, M. bovis may invade specific T-cell subsets and induce host generation of exhausted T-cells, which helps it to escape immune clearance. Moreover, the M. bovis antigen exhibits high-frequency variation in size and expression period, which allows it to avoid activation of the host humoral immune response. This review includes some recent advances in studying the immune response to M. bovis. These may help to further understand the host immune response against M. bovis and to develop potential therapeutic approaches to control M. bovis infection.

Mycoplasma bovis Mastitis

“…Upon interaction with the epithelial cells, M. bovis induces the production of proinflammatory cytokines such as interleukin (IL) −1β, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). This non-specific innate immune response can attack the invading pathogens as the first line of defense, resulting in a subsequent cascade of events, including antigen presentation by the dendritic cells, CD4 cells activation, and differentiation into T-helper cells Th1, Th2, Th17, and regulatory T cells (Treg) ( Askar et al., 2021 Jimbo et al., 2017 ; Kauf et al., 2007 ; Zbinden et al., 2015 ;). During an intramammary challenge of cows with M. bovis , the initial reaction of the host was demonstrated to be increased SCC 66 h post-infection and synthesis of acute-phase proteins at 108 h post-infection ( Kauf et al., 2007 ).…”

“…Cellular responses involve Th1 cells, which activate CD8 cytotoxic T-cells and macrophages through interferon-gamma (IFN-γ) and TNF-α to degrade the mycoplasmas or cause apoptosis ( Askar et al., 2021 ). Interleukin 12, which mediates the differentiation of T-cells into Th1 was reported to be increased in mRNA profiling of M. bovis infected PBMCs ( Askar et al., 2021 Gondaira et al., 2015 ;). Interferon-gamma (IFN-γ) and TNF-α have been shown to be elevated both in vitro in neutrophils and in vivo during intramammary M. bovis infection ( Jimbo et al., 2017 Kauf et al., 2007 ;).…”

“…Th17 cells produce IL-17 and IL-22, which enhance the recruitment of neutrophils, also play a key role ( Annunziato et al., 2015 Askar et al., 2021 ;). Mycoplasma bovis , however, causes persistent immunosuppression by repressing neutrophil activity, the first line of cellular defense against pathogens ( Thomas et al., 1990 , 1991 ).…”

Fatal Calf Pneumonia Outbreaks in Italian Dairy Herds Involving Mycoplasma bovis and Other Agents of BRD Complex

“…After infection, M. bovis can spread through the bloodstream, establishing a long-term persistent infection through escaping the immune response. M. bovis, as primary agent or under the action of concomitant stressing factors such as weaning, transport, or relocation to feedlots, may impair the host immune system efficiency resulting in the onset of the disease (6) including severe, often fatal, pneumonia (7,8). Case fatality is estimated to be 5-10% or higher in more severe cases, with morbidity reaching 35% (3).…”

Genes and regulatory mechanisms associated with experimentally-induced bovine respiratory disease identified using supervised machine learning methodology

“…As discussed by Behura and colleagues 31 , these infected cattle may have been euthanized and sample collected too early in the course of BRD to detect immunological changes. Additionally, Mycoplasma bovis is capable of evading the host immune response, specifically neutrophilic responses, and may lead to the development of T-cell “exhaustion” that eventually culminates in severe clinical disease 95 . Future transcriptomic evaluation of single cells or the sub-cellular space, instead of bulk tissue samples, may better elucidate mechanisms associated with Mycoplasma bovis .…”