Alterations in cytokines and effects of dexamethasone immunosuppression during subclinical infections of invasive Klebsiella pneumoniae with hypermucoviscosity phenotype in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques

Abstract

Invasive Klebsiella pneumoniae with the hypermucoviscosity phenotype (HMV K. pneumoniae) is an emerging human pathogen that also has been attributed to fatal multisystemic disease in African green monkeys at our institution. Combining a cluster of subclinically infected macaques identified in March and April 2008 and the animals documented during a subsequent survey of more than 300 colony nonhuman primates yielded a total of 9 rhesus macaques and 6 cynomolgus macaques that were subclinically infected. In an attempt to propagate the responsible HMV K. pneumoniae strain, a subset of these animals was immunosuppressed with dexamethasone. None of the treated animals developed clinical disease consistent with the multisystemic disease that affected colony African green monkeys. However, cytokine analysis revealed significant alterations of secreted cytokines in macaques subclinically infected with HMV K. pneumoniae when compared with noninfected macaques, thereby calling into question the suitability of animals subclinically infected with HMV K. pneumoniae for use in immunologic or infectious disease research.

Figure 1.

Cytokine levels (geometric mean; bar, SEM) in macaques before immunosuppression. (A) Cynomolgus macaques showed significant (*, P ≤ 0.05) differences between groups for granulocyte–macrophage colony-stimulating factor (GM-CSF), IL10, IL6, and IL8. (B) Rhesus macaques showed significant (*, P ≤ 0.05) differences between groups for IL6 and IL8.

Figure 2.

IL8 levels (geometric mean; bar, SEM) in cynomolgus macaques after immunosuppression. Levels differed significantly (P < 0.05) between groups.

Figure 3.

IL8 levels (geometric mean; bar, SEM) in rhesus macaques after immunosuppression. Levels differed significantly (P < 0.05) between groups.

Figure 4.

Mesenteric lymph node from a glucocorticoid -treated macaque. Note the diffuse paucity of lymphoid tissue (lymphoid atrophy). Hematoxylin and eosin stain; magnification, ×4.

Figure 5.

Adrenal gland from a glucocorticoid-treated macaque (left) shows diffuse atrophy of zona fascicularis, with only a small portion (boxed area) remaining. Adrenal gland from a nonimmunosuppressed macaque (right). F, zona fascicularis; G, zona glomerulosa; R, zona reticularis. Hematoxylin and eosin stain; magnification, ×20.

Figure 6.

Stomach from a nonimmunosuppressed macaque. Note the helical agyrophilic bacteria (arrows) lining the gasteric epithelium. Warthin-Starry silver stain; magnification, ×40.