Abstract
Gram‐negative bacteria (GNB) emerge as important pathogens causing pulmonary infection, which can develop into sepsis due to bacterial resistance to antibiotics. GNB pneumonia poses a huge social and economic burden all over the world. During GNB infection in the lung, Toll‐like receptor 4 (TLR4) can form a complex with MD2 and CD14 after recognizing lipopolysaccharide of GNB, initiate the MyD88‐ and TRIF‐dependent signalling pathways and stimulate host non‐specific immune response. In this review, we summarize recent progress in our understanding of the role of TLR4 in GNB pneumonia. The latest experimental results, especially in TLR4 knockout animals, suggest a promising potential of targeting TLR4 signalling pathway for the treatment of GNB pneumonia. Furthermore, we highlight the benefits of Traditional Chinese Medicine as novel candidates for the therapy of GNB pneumonia due to the modulation of TLR4 signalling pathway. Finally, we discuss the promise and challenge in the development of TLR4‐based drugs for GNB pneumonia.
Highlights
Streptococcus pneumoniae is a main cause of pneumonia, followed by other Gram‐positive bacteria such as Staphylococcus aureus and Bacillus anthracis
The missense mutations D299G and T399I were associated with LPS hypo‐responsiveness and increased susceptibility to infection by Gram‐negative bac‐ teria (GNB), and the underlying mechanism may be due to the fact that D299G polymorphism could damage the recruitment of myeloid differentiation factor 88 (MyD88) and taining adaptor inducing interferon IFN‐β (TRIF) to Toll‐like receptor 4 (TLR4) and the subsequent activation of downstream signalling pathway.[46]
Based on all the above discussion, it is undoubted that TLR4 plays an important role in GNB pneumonia
Summary
Streptococcus pneumoniae is a main cause of pneumonia, followed by other Gram‐positive bacteria such as Staphylococcus aureus and Bacillus anthracis. Toll‐like receptor 4 plays a crucial role in mediating innate immune responses to infections in pneumonia, especially to GNB infection.
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