During bacterial infection, PD-1 expression could be induced by antigen-dependent stimulation such as IgM crosslinking on B cells, TCR-mediated activation of CD4+ T cells, by bacteria pathogen-associated molecular patterns, such as lipopolysaccharide, which in mice activates both B cells and macrophages, or by inflammatory cytokines IL-1β, IL-6, and TNF-α [62, 63]. Here, CD4 is linked to bacterial infectious disease.