SP-A Preserves Airway Homeostasis During Mycoplasma pneumoniae Infection in Mice

Abstract

The lung is constantly challenged during normal breathing by a myriad of environmental irritants and infectious insults. Pulmonary host defense mechanisms maintain homeostasis between inhibition/clearance of pathogens and regulation of inflammatory responses that could injure the airway epithelium. One component of this defense mechanism, surfactant protein-A (SP-A), exerts multifunctional roles in mediating host responses to inflammatory and infectious agents. SP-A has a bacteriostatic effect on Mycoplasma pneumoniae (Mp), which occurs by binding surface disaturated phosphatidylglycerols. SP-A can also bind the Mp membrane protein, MPN372. In this study we investigated the role of SP-A during acute phase pulmonary infection with Mp using mice deficient in SP-A. Biologic responses, inflammation and cellular infiltration, were much greater in Mp infected SP-A−/− mice than wild type mice. Likewise, physiologic responses (airway hyperresponsiveness and lung compliance) to Mp infection were more severely affected in SP-A−/− mice. Both Mp-induced biologic and physiologic changes were attenuated by pharmacologic inhibition of TNF-α. Our findings demonstrate that SP-A is vital to preserving lung homeostasis and host defense to this clinically relevant strain of Mp by curtailing inflammatory cell recruitment and limiting an overzealous TNF-α response.

Surfactant Protein-A Inhibits Mycoplasma-Induced Dendritic Cell Maturation through Regulation of HMGB-1 Cytokine Activity

“…For in vivo infection, adherent Mp were washed by centrifuging at 6000 rpm for 5 minutes and resuspended in sterile saline for infection at a concentration of 1 × 10 8 Mp/50 μl inoculum. Mp burden was assessed as previously described by plating BAL or by RT-PCR using primers against Mp-specific P1-adhesin gene relative to the housekeeper cyclophilin (6). …”

“…Indeed, studies have demonstrated that surfactant protein A (SP-A) binds Mp though disaturated phosphatidylglycerols and through a specific surface binding protein, MPN372 (4, 5) and limits the growth of Mp in vitro (5). SP-A also helps maintain airway homeostasis and reduce hyperresponsiveness by curtailing an overly-ambitious pro-inflammatory immune response during Mp infection in mice in vivo (6). …”

Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

“…In contrast, mice infected with Eap Ϫ S. aureus that is not recognized by SP-A displayed impaired killing and persistent infection in association with elaboration of low but unsustainable levels of TNF␣, more intense neutrophilic inflammation, and delayed repopulation of the lung with macrophages. Previous studies reported that SP-A mediates both clearance and restoration of alveolar immune homeostasis in mice infected with Mycoplasma pneumoniae (83). However, the relative importance of SP-A binding to macrophages or bacteria has not been clear because SP-A may have indirect activities on macrophages.…”

Pulmonary Surfactant: An Immunological Perspective

“…In contrast, SP-A and SP-D suppress secretion of pro-inflammatory cytokines and oxidant intermediates when macrophages are challenged with pathogen-derived cell wall components such as lipopolysaccharide [121,[138][139][140][141][142][143][144] or mycobacterial cell wall extract [145]; this protective SP-A function has been noted in both in vitro macrophage culture and in vivo animal models [58,140,146]. SP-A initially enhances clearance of Mycoplasma pneumoniae [133,134] but subsequently turns off inflammation [146], indicating that SP-A works in a temporal fashion to resolve inflammation. In this context, SP-A and SP-D regulate phagocytosis of apoptotic cells [147,148].…”