title: Aspergillus flavus induces granulomatous cerebral aspergillosis in mice with display of distinct cytokine profile.
abstract: Aspergillus flavus is one of the leading Aspergillus spp. resulting in invasive aspergillosis of central nervous system (CNS) in human beings. Immunological status in aspergillosis of central nervous system remains elusive in case of both immunocompetent and immunocompromised patients. Since cytokines are the major mediators of host response, evaluation of disease pathology along with cytokine profile in brain may provide snapshots of neuro-immunological response. An intravenous model of A. flavus infection was utilized to determine the pathogenicity of infection and cytokine profile in the brain of male BALB/c mice. Enumeration of colony forming units and histopathological analyses were performed on the brain tissue at distinct time periods. The kinetics of cytokines (TNF-α, IFN-γ, IL-12/IL-23p40, IL-6, IL-23, IL-17A and IL-4) was evaluated at 6, 12, 24, 48, 72 and 96h post infection (hPI) in brain homogenates using murine cytokine specific enzyme linked immunosorbent assay. Histological analysis exhibited the hyphae with leukocyte infiltrations leading to formation of granulomata along with ischemia and pyknosis of neurons in the brain of infected mice. Diseased mice displayed increased secretion of IFN-γ, IL-12p40 and IL-6 with a concomitant reduction in the secretion of Th2 cytokine IL-4, and Th17 promoting cytokine, IL-23 during the late phase of infection. A.flavus induced inflammatory granulomatous cerebral aspergillosis in mice, characterized by a marked increase in the Th1 cytokines and neurons undergoing necrosis. A marked increase in necrosis of neurons with concurrent inflammatory responses might have led to the host mortality during late phase of infection.
authors: Infectious Diseases Laboratory, National Institute of Immunology, New Delhi 110067, India. Electronic address: rajesh.anand@nii.ac.in.
authors: R
authors: R
authors: Anand
authors: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Solan, HP 173234, India.
authors: J
authors: J
authors: Shankar
authors: Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, C.G. 495009, India.
authors: B N
authors: BN
authors: Tiwary
authors: Infectious Diseases Laboratory, National Institute of Immunology, New Delhi 110067, India. Electronic address: singhap@nii.ac.in.
authors: A P
authors: AP
authors: Singh
mesh_terms: D000818:Animals; D001231:Aspergillus flavus / Q000302:isolation & purification; D001921:Brain / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006099:Granuloma / Q000276:immunology* / Q000473:pathology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C / Q000378:metabolism; D020953:Neuroaspergillosis / Q000276:immunology* / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Aspergillus flavus; Cerebral aspergillosis; Cytokines; Granuloma; Neuropathogenesis