Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis
- 27 May 2003
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 33 (6), 1744-1753
- https://doi.org/10.1002/eji.200323626
Abstract
Neutrophils are generally considered to contribute to host defense through their potent microbicidal activity. However, there is accumulating evidence that neutrophils also have an important regulatory role in establishing the balance of Th1 and Th2 responses. This study investigated the role of neutrophils in defense against pulmonary Cryptococcus neoformans infection using neutrophil-depleted BALB/c mice generated by administering mAb RB6–8C5. Neutropenic mice with pulmonary infection survived significantly longer than control mice, but there was no difference between groups infected intravenously. On day 1 of infection, neutropenic mice had significantly smaller fungal burdens than control mice. On day 7, neutropenic mice had significantly higher lung concentrations of IL-10, TNF-α, IL-4, and IL-12 than control mice, but there was no difference in IFN-γ and MCP-1 levels. Neutrophils influenced the outcome of cryptococcal infection in mice through mechanisms that did not involve a reduction in early fungal burden. The absence of neutrophils in lung tissue during the initial stages of infection appeared to alter the inflammatory response in a manner thatwas subsequently beneficial to the host. Higher levels of Th1- and Th2-associated cytokines in neutropenic mice could have simultaneously promoted a strong cellular response while reducing inflammatory damage to the lung. Our results support the emerging concept that neutrophils play an important function in modulating the development of the immune response.Keywords
This publication has 50 references indexed in Scilit:
- Induction of Interleukin-12 and Gamma Interferon Requires Tumor Necrosis Factor Alpha for Protective T1-Cell-Mediated Immunity to PulmonaryCryptococcus neoformansInfectionInfection and Immunity, 2002
- Both Th1 and Th2 Cytokines Affect the Ability of Monoclonal Antibodies To Protect Mice againstCryptococcus neoformansInfection and Immunity, 2001
- Anti-inflammatory Activity of IVIG Mediated Through the Inhibitory Fc ReceptorScience, 2001
- Human Neutrophil-Mediated Nonoxidative Antifungal Activity againstCryptococcus neoformansInfection and Immunity, 2000
- The neutrophil as a cellular source of chemokinesImmunological Reviews, 2000
- Polymorphonuclear Neutrophils Are Necessary for the Recruitment of CD8+T Cells in the Liver in a Pregnant Mouse Model ofChlamydophila abortus(Chlamydia psittaciSerotype 1) InfectionInfection and Immunity, 2000
- Neutrophils are involved in the non‐specific resistance to listeriosis induced by mycobacterial infectionsImmunology, 1996
- Neutrophils are essential for early anti-Listeria defense in the liver, but not in the spleen or peritoneal cavity, as revealed by a granulocyte-depleting monoclonal antibody.The Journal of Experimental Medicine, 1994
- Factors Influencing Killing of Cryptococcus neoformans by Human Leukocytes In VitroThe Journal of Infectious Diseases, 1972
- Mechanisms of Native and Acquired Resistance to Infection withCryptococcus NeoformansCRC Critical Reviews in Microbiology, 1972