Heat shock proteins generate β-chemokines which function as innate adjuvants enhancing adaptive immunity

HSP70 Enhances Macrophage Phagocytosis by Interaction With Lipid Raft-Associated TLR-7 and Upregulating p38 MAPK and PI3K Pathways

“…Tissue lysis releases these abundant cellular proteins into the extracellular compartment which, in turn, prepares the antigen presenting cells (APCs), including macrophages for microbial invasion [3,4]. Immunologically, HSPs stimulate APCs (macrophages and dendritic cells) to secrete cytokines [3,5,6], chemokines [7], nitric oxide [8], and induce expression of selected cell-surface markers to high levels [3,9]. HSPs chaperone and present antigenic peptides activating a powerful immune response [10 -14].…”

Expression and regulation of chemokines in mycobacterial infection

“…It has also been demonstrated that M. tuberculosis HSP70 stimulates human macrophages to produce CCchemokines. 69 Even though BCG may not protect adults against pulmonary tuberculosis, it still confers good protection against disseminated tuberculosis and tuberculous meningitis in children. Furthermore, BCG provides efficient cross-protection against leprosy, and this vaccine is used for treatment of certain chronic diseases, including cancer.…”

Functional domains of HSP70 stimulate generation of cytokines and chemokines, maturation of dendritic cells and adjuvanticity

“…We postulated that the adjuvanticity of mHSP70 is accounted for by the stimulation of production of the CC chemokines CCL3, CCL4 and CCL5, which attract the entire repertoire of immunological cells [12]. Since both the major co-stimulatory pathways CD80/86-CD28 and CD40-CD40L stimulate these CC chemokines [13][14][15], we explored the possibility that HSPs interact with one of the co-stimulatory molecules [2].…”

“…Indeed, mHSP70 and HSP96 can be fused or covalently linked or loaded with peptides to elicit specific immunity to tumours or viruses [25][26][27][28]. The adjuvanticity of mHSP70 has been demonstrated not only by systemic immunization but also by mucosal immunization in non-human primates [12]. Both systemic and mucosal adjuvanticities are dependent on the stimulation of production of three CC chemokines, CCL3, CCL4 and CCL5.…”