Myeloid expression of the AP‐1 transcription factor JUNB modulates outcomes of type 1 and type 2 parasitic infections

Abstract

Activation of macrophages is a key step in initiation of immune responses, but the transcriptional mechanisms governing macrophage activation during infection are not fully understood. It was recently shown that the AP-1 family transcription factor JUNB positively regulates macrophage activation in response to Toll-like receptor agonists that promote classical or M1 polarization, as well as to the cytokine Interleukin-4 (IL-4), which elicits an alternatively activated or M2 phenotype. However, a role for JUNB in macrophage activation has never been demonstrated in vivo. Here, to dissect the role of JUNB in macrophage activation in a physiological setting, mice lacking JUNB specifically in myeloid cells were tested in two infection models: experimental cerebral malaria, which elicits a pathological type 1 immune response, and helminth infection, in which type 2 responses are protective. Myeloid-restricted deletion of Junb reduced type 1 immune activation, which was associated with reduced cerebral pathology and improved survival during infection with Plasmodium berghei. Myeloid JUNB deficiency also compromised type 2 activation during infection with the hookworm Nippostrongylus brasiliensis, leading to diminished cytokine production and eosinophil recruitment and increased parasite burden. These results demonstrate that JUNB in myeloid cells shapes host responses and outcomes during type 1 and type 2 infections.

A Novel lncRNA Regulates the Toll-Like Receptor Signaling Pathway and Related Immune Function by Stabilizing FOS mRNA as a Competitive Endogenous RNA

“…Some studies have found that an appropriately high expression of AP-1 can enhance the body's immune and antibacterial ability and improve its ability to respond to multiple stimuli (56). The AP-1 family of transcription factors can activate Toll-like receptor agonists and positively regulate interleukin-4 (IL-4) to activate macrophages, thereby enhancing antibacterial activity (57). AP-1 plays a key role in regulating immunity as an intermediate regulatory factor; for example, CR3 and Dectin-1 synthesize macrophage cytokines through synergistic activation of the lipid and Syk-JNK-AP-1 pathways (58).…”

Regulation of host immune cells and cytokine production induced byTrichinella spiralisinfection

“…The immune mechanism of parasitic diseases mainly involves the interaction of Th1 and Th2 reactions and related cytokines, which inhibits their reproduction and amplification [11]. Th1 cells mainly secrete IFN-γ to regulate cellular immunity and mediate cellular immune response.…”

Quantitative proteomic analysis of host epithelial cells infected by Salmonella enterica serovar Typhimurium

“…While most AP‐1 proteins are considered to be oncogenic, JunB was shown to have anti‐oncogenic effects . Other studies suggest the involvement of JunB in the inhibition of apoptosis and the activation of host immune responses during parasite infection . As a zinc finger transcription factor, SP1 regulates a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses .…”