Microbiological and Inflammatory Factors Associated with the Development of Pneumococcal Pneumonia

Abstract

Pneumococcal pneumonia still is associated with a high mortality rate, despite appropriate antimicrobial therapy. Many gaps remain in the understanding of the pathogenesis of this deadly infection. The microbial and inflammatory events that characterize survival or death after intranasal inoculation of mice with an LD(50) inoculum of Streptococcus pneumoniae were investigated. Survival was associated with rapid bacterial clearance and low inflammation (surfactant and red blood cells in alveoli), but no neutrophil recruitment or lung tissue injury was noted. By contrast, death was preceded by strong bacterial growth that peaked 48 h after the infection and was associated with gradual increases in pulmonary levels of interleukin-6, macrophage inflammatory protein (MIP)-1alpha, MIP-2, monocyte chemoattractant protein-1, KC, and neutrophil recruitment. The injection of tumor necrosis factor-alpha or the addition of lipopolysaccharide or heat-killed S. pneumoniae to the inoculum enhanced early host response and survival. These observations may help develop appropriate markers of evolution of pneumonia, as well as new therapeutic strategies.

Role of Galectin-3 in Leukocyte Recruitment in a Murine Model of Lung Infection by Streptococcus pneumoniae

“…Because the numbers of macrophages were similar in both types of mice and alveolar macrophages do not play a critical role in the clearance of S. pneumoniae (58), this increase in bacterial burden is likely due to the reduced number of neutrophils recruited to the alveoli. Indeed, Dallaire et al previously reported that the number of bacteria in the lungs is closely correlated with pulmonary cytokine/chemokine levels, and with neutrophil recruitment in streptococcal pneumonia models (60). The reduced recruitment of neutrophils into S. pneumonia-infected alveoli of galectin-3 null mice was partially restored to the level of WT when galectin-3 was instilled to the infected alveoli.…”

Streptococcus pneumoniaesecretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells

“…During pneumococcal pneumonia, there is persistent infiltration of inflammatory immune cells in the lungs that could themselves produce DNA-damaging RONS (6)(7)(8). Hence, inflammation-driven collateral damage to pulmonary cell DNA is plausible during S. pneumoniae infection.…”

“…S. pneumoniae is known to induce a robust inflammatory response at the site of infection that culminates with infiltration and accumulation of inflammatory cells including neutrophils and macrophages (6)(7)(8).…”

<i>Mycoplasma pneumoniae</i> pneumonia, bacterial pneumonia and viral pneumonia

“…Kyung-Yil Lee 1 , You-Sook Youn 2 , Jae-Wook Lee 2 , Jin-Han Kang 1 A pneumonia é uma das doenças mais frequentes tratadas por pediatras. A maioria dos pacientes com pneumonia recupera-se sem complicações, como ocorre com as doenças autolimitadas.…”

“…Nas lesões iniciais causadas pela pneumonia, os neutrófilos ativados e os fagócitos mononucleares predominam. Já os mediadores, tais como as enzimas proteolíticas, os radicais de oxigênio e as citocinas dessas células podem estar associados com lesões pulmonares do hospedeiro 1 . Na pneumonia por micoplasma (Mycoplasma pneumoniae -MP) e nas pneumonias virais que aparecem juntamente com o sarampo, a síndrome respiratória aguda grave (SRAG) e a influenza, os pacientes apresentam leucopenia com linfopenia.…”