The Role of Lipoproteins in Mycoplasma-Mediated Immunomodulation

Abstract

Mycoplasma infections, such as walking pneumonia or pelvic inflammatory diseases, are a major threat to public health. Despite their relatively small physical and genomic size, mycoplasmas are known to elicit strong host immune responses, generally inflammatory, while also being able to evade the immune system. The mycoplasma membrane is composed of approximately two-thirds protein and one-third lipid and contains several lipoproteins that are known to regulate host immune responses. Herein, the immunomodulatory effects of mycoplasma lipoproteins are reviewed. A better understanding of the immunomodulatory effects, both activating and evasive, of Mycoplasma surface lipoproteins will contribute to understanding mechanisms potentially relevant to mycoplasma disease vaccine development and treatment.

Keywords: immune modulation; immune system; inflammation; lipoproteins; mycoplasma.

FIGURE 1

Mechanisms of actions of mycoplasmal lipoproteins: Mycoplasmal lipoproteins lead to inflammatory responses and immune system activation through direct effects on both epithelial and immune cells. Initial adhesion to epithelia of respiratory tract is mediated through adhesins such as P1 (MPN141) as well as other accessory proteins. Epithelial cell activation as well as mycoplasmal lipoproteins induce secretion of chemokines such as IL-8 that promote neutrophilic infiltration and activation of neutrophils (through several mechanisms including NETosis). Neutrophilic activation is followed by activation of myeloid cells (monocytes, macrophages, dendritic cells) that ultimately leads to activation of adaptive immunity (lymphocytes). A key family of receptors that play an important role in recognizing, and inducing responses to Mycoplasmal lipoproteins are the Toll-Like Receptors (TLRs such as TLR2 and TLR6) that are key players in inflammatory responses upon infection. Mycoplasmal lipoproteins can also activate cells through the inflammasome and the pre-cursors of proinflammatory cytokines, such as IL-1β and IL-18, can be cleaved and activated in a caspase-dependent manner prior to their release. Non-TLR or inflammasome dependent mechanisms by which Mycoplasmal lipoproteins can lead to inflammatory responses and immune activation also exist (such as autophagy). TLRs (such as TLR-2 and TLR-6), also play an important role in inducing apoptosis in both monocyte and lymphocyte cell lines through induction of p38 MAPK, the apoptosis signal-regulating kinase (ASK1), caspase and the NF-kB pathways and the release of Nitric Oxide from macrophages. See text for further details. Given poorly understood mechanisms, further studies are needed to elucidate the mechanisms of immunomodulation mediated by mycoplasmal lipoproteins.