2008
DOI: 10.1128/iai.00341-08
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Enhanced Innate Immune Responsiveness to PulmonaryCryptococcus neoformansInfection Is Associated with Resistance to Progressive Infection

Abstract: Genetically regulated mechanisms of host defense against Cryptococcus neoformans infection are not well understood. In this study, pulmonary infection with the moderately virulent C. neoformans strain 24067 was used to compare the host resistance phenotype of C57BL/6J with that of inbred mouse strain SJL/J. At 7 days or later after infection, C57BL/6J mice exhibited a significantly greater fungal burden in the lungs than SJL/J mice. Characterization of the pulmonary innate immune response at 3 h after cryptoco… Show more

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Cited by 63 publications
(72 citation statements)
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“…Preserved production of other CCR2 agonists, such as MCP-2 and MCP-3, may have compensated for the defective production of MCP-1. Because dendritic cells and alveolar macrophages play a critical role in the early innate protective host response against C. neoformans (71) and are associated with natural resistance to progressive infection (62), it is likely that functional defects of these cell populations also contributed to the increased susceptibility of the Tg mice to C. neoformans infection. Blood monocytes and alveolar macrophages from HIV-infected patients have impaired fungistatic activity against C. neoformans (72)(73)(74)(75)(76).…”
Section: Discussionmentioning
confidence: 99%
“…Preserved production of other CCR2 agonists, such as MCP-2 and MCP-3, may have compensated for the defective production of MCP-1. Because dendritic cells and alveolar macrophages play a critical role in the early innate protective host response against C. neoformans (71) and are associated with natural resistance to progressive infection (62), it is likely that functional defects of these cell populations also contributed to the increased susceptibility of the Tg mice to C. neoformans infection. Blood monocytes and alveolar macrophages from HIV-infected patients have impaired fungistatic activity against C. neoformans (72)(73)(74)(75)(76).…”
Section: Discussionmentioning
confidence: 99%
“…The lung lobes were inflated under constant pressure (25 cm H 2 O) with 10% neutral buffered formalin (Sigma-Aldrich), excised, and embedded in paraffin for histopathology. In the second experiment, mouse tracheas were cannulated, and four volumes of 0.5-ml cold sterile saline were instilled through the tracheal cannula, withdrawn, and pooled to recover bronchoalveolar lavage fluids (BALF), as previously described (38). In the third experiment, lungs were perfused with cold saline, flash frozen, and stored at 280˚C until processing for viral titer determination or RNA isolation.…”
Section: Infection Of Mice Definition Of Phenotype and Tissue Collementioning
confidence: 99%
“…The most notable finding from the phenotypic survey was that C5-sufficient C3H/HeN mice were highly susceptible to C. neoformans infection, with a lung fungal burden that was similar to that of C57BL/6J mice (mean lung burden, 6.49 Ϯ 0.10 log 10 CFU versus 6.94 Ϯ 0.16 log 10 CFU) (22). The marked susceptibility of C3H/HeN mice compared to that of resistant CBA/J mice (mean lung burden, 4.27 Ϯ 0.27 log 10 CFU) was particularly striking since these strains are closely related and share the H-2 k/k haplo-type that mediates antigen presentation by the immune system (17,18). C3H/HeN is susceptible to progressive C. neoformans infection.…”
Section: Resultsmentioning
confidence: 99%
“…At day 14 after C. neoformans infection, C3H/HeN mice also developed significantly higher airway and lung tissue eosinophilia, while CBA/J mice mounted a neutrophilic response. Pulmonary eosinophilia is a marker of a Th2 response and has been associated with chronic or progressive cryptococcal infection (21), while airway and lung tissue neutrophilia is characteristic of resistant inbred strains such as SJL/J and CBA/J (17). Despite these associations, the role of these inflammatory cell subsets in host defense against C. neoformans is complex.…”
Section: Fig 8 Effect Ofmentioning
confidence: 99%
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