Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis

Eur J Immunol. 2003 Jun;33(6):1744-53. doi: 10.1002/eji.200323626.


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-alpha, IL-4, and IL-12 than control mice, but there was no difference in IFN-gamma 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 that was 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemokine CCL2 / biosynthesis
  • Chemotaxis, Leukocyte
  • Cryptococcosis / immunology*
  • Cryptococcosis / microbiology
  • Cryptococcus neoformans / isolation & purification
  • Cytokines / biosynthesis*
  • Female
  • Immunity, Innate
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-12 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Lung / metabolism*
  • Lung / microbiology
  • Lung / pathology
  • Lung Diseases, Fungal / immunology*
  • Lung Diseases, Fungal / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Neutropenia / metabolism*
  • Phagocytosis
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Chemokine CCL2
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma