Monocyte chemoattractant protein 1 does not contribute to protective immunity against pneumococcal pneumonia

Abstract

To determine the role of monocyte chemoattractant protein 1 (MCP-1) during pneumococcal pneumonia, MCP-1 knockout and wild-type mice were infected with Streptococcus pneumoniae. Pulmonary MCP-1 levels were strongly correlated to bacterial loads in wild-type mice. However, MCP-1 knockout and wild-type mice were indistinguishable with respect to bacterial growth, inflammatory responses, and lethality.

FIG. 1.

MCP-1 production. (A) Correlation between pulmonary MCP-1 levels and bacterial load during pneumococcal pneumonia. MCP-1 levels and bacterial loads in whole lung homogenates from WT mice 48 h after inoculation with 4 × 10³ to 50 × 10³ S. pneumoniae CFU. The closed line represents curve fit; the dashed line represents the 95% confidence band. Goodness of fit is presented as R². (B) MCP-1 production in MLE-12 cell line and mouse macrophages. MLE-12 and mouse macrophages (MΦ) incubated with either medium (black bars) or HKSP (white bars). *, P < 0.05. Data are means ± SEM (n = 4 to 5 per group).

FIG. 2.

MCP-1 deficiency does not influence bacterial growth or survival during pneumococcal pneumonia. (A) Bacterial loads in whole-lung homogenates 5, 24, and 48 h after inoculation with 5 × 10⁴ S. pneumoniae CFU in WT (black bars) and MCP-1 KO mice (open bars). Bacterial loads in whole-lung homogenates (B and C) and survival (D and E) of WT (black bars or symbols) and MCP-1 KO mice (open bars or symbols) inoculated with 10⁴ CFU (B and D) or 4 × 10³ CFU (C and E). BC+ indicates the number of positive blood cultures. Data are means ± SEM (n = 6 to 8 per group [A, B, and C]; n = 10 to 12 per group [D and E]).

FIG. 3.

MCP-1 deficiency does not influence cytokine or chemokine concentrations. Levels of cytokines (IL-6, TNF-α) and chemokines (KC, MIP-2) in whole-lung homogenates and cytokine concentrations in plasma obtained from WT (black bars) and MCP-1 KO (white bars) mice after infection with 5 × 10⁴ S. pneumoniae CFU. Data are means ± SEM (n = 6 to 8 per group).