Streptococcus pneumoniae is the main cause of bacterial pneumonia, a condition that currently produces significant global morbidity and mortality. The initial immune response to this bacterium occurs when the innate system recognizes common motifs expressed by many pathogens, events driven by pattern recognition receptors like the Toll-like family receptors (TLRs). In this study, lung myeloid-cell populations responsible for the innate immune response (IIR) against S. pneumoniae, and their dependence on the TLR4-signaling axis, were analyzed in TLR4^–/– and Myeloid-Differentiation factor-88 deficient (MyD88^–/–) mice. Neutrophils and monocyte-derived cells were recruited in infected mice 3-days post-infection. Compared to wild-type mice, there was an increased bacterial load in both these deficient mouse strains and an altered IIR, although TLR4^–/– mice were more susceptible to bacterial infection. These mice also developed fewer alveolar macrophages, weaker neutrophil infiltration, less Ly6C^high monocyte differentiation and a disrupted classical and non-classical monocyte profile. The pro-inflammatory cytokine profile (CXCL1, TNF-α, IL-6, and IL-1β) was also severely affected by the lack of TLR4 and no induction of Th1 was observed in these mice. The respiratory burst (ROS production) after infection was profoundly dampened in TLR4^–/– and MyD88^–/– mice. These data demonstrate the complex dynamics of myeloid populations and a key role of the TLR4-signaling axis in the IIR to S. pneumoniae, which involves both the MyD88 and TRIF (Toll/IL-1R domain-containing adaptor-inducing IFN-β) dependent pathways.

肺炎链球菌是细菌性肺炎的主要原因，目前这种疾病在全球范围内造成很高的发病率和死亡率。当先天系统识别出许多病原体表达的共同基序时，就会发生针对这种细菌的初始免疫反应，这些事件是由模式识别受体（如 Toll 样家族受体 (TLR)）驱动的。在这项研究中，负责先天免疫反应（IIR）的肺髓细胞群肺炎链球菌及其对 TLR4 信号轴的依赖性，在 TLR4 ^–/–和骨髓分化因子 88 缺陷 (MyD88 ^–/– ) 小鼠中进行了分析。感染后3天，在受感染的小鼠体内招募中性粒细胞和单核细胞衍生的细胞。^{与野生型小鼠相比，尽管 TLR4 –/–}小鼠更容易受到细菌感染，但这些缺陷小鼠品系的细菌载量有所增加，并且 IIR 发生了改变。这些小鼠还出现了较少的肺泡巨噬细胞、较弱的中性粒细胞浸润、较少的 Ly6C^高单核细胞分化以及破坏的经典和非经典单核细胞谱。促炎细胞因子谱（CXCL1、TNF-α、IL-6 和 IL-1β）也因 TLR4 的缺乏而受到严重影响，并且在这些小鼠中没有观察到 Th1 的诱导。^{TLR4 –/–}和 MyD88 ^–/–小鼠感染后的呼吸爆发（ROS 产生）受到严重抑制。这些数据证明了骨髓细胞群的复杂动态以及 TLR4 信号轴在 IIR 中的关键作用肺炎链球菌，其中涉及 MyD88 和 TRIF（包含 Toll/IL-1R 结构域的接头诱导 IFN-β）依赖性途径。