Adjunctive immunotherapy with recombinant cytokines for the treatment of disseminated candidiasis  F.L. van de Veerdonk, B.-J. Kullberg, M.G. Netea  Clinical Microbiology and Infection  Volume 18, Issue 2, Pages 112-119 (February 2012) DOI: 10.1111/j.1469-0691.2011.03676.x Copyright © 2012 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 1 Host defence against systemic Candida infections is mediated through a combination of cellular and humoral immune mechanisms that act in concert to recognize and eliminate the invading pathogen. The first cells to encounter the invading C. albicans are the tissue macrophages. They release chemokines and proinflammatory cytokines that lead to recruitment and activation of blood neutrophils and inflammatory monocytes, which, in turn, phagocytose and kill the fungus. Later, adaptive immune mechanisms such as Th1 and Th17 cellular responses, or humoral antibody formation, are also induced. IFN, interferon; IL, interleukin; Mf, macrophage; NK, natural killer cell; NO, nitric oxide; PMN, polymorphonuclear neutrophil; Th, T-helper lymphocyte; TNF, tumour necrosis factor. Clinical Microbiology and Infection 2012 18, 112-119DOI: (10.1111/j.1469-0691.2011.03676.x) Copyright © 2012 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 2 The role of proinflammatory cytokines during sepsis: whereas proinflammatory cytokines are overwhelmingly released during acute meningococcal sepsis, the concentrations found during systemic candidiasis are much lower. This is partly because of differences in microbial load in the two infections. It is therefore late-stage immunoparalysis, rather than the acute cytokine storm, that is the main immunological disturbance in systemic candidiasis, and the patient would benefit from enhancement of the host defence. LPS, lipopolysaccharide; Mo/Mf, monocyte/macrophage; rGM-CSF, recombinant granulocyte–macrophage colony-stimulating factor; rIFN-γ, recombinant interferon-γ; SIRS, systemic inflammatory response syndrome; Th, T-helper lymphocyte. Clinical Microbiology and Infection 2012 18, 112-119DOI: (10.1111/j.1469-0691.2011.03676.x) Copyright © 2012 European Society of Clinical Infectious Diseases Terms and Conditions