A 20-Mer Peptide Derived from the Lectin Domain of SP-A2 Decreases Tumor Necrosis Factor Alpha Production during Mycoplasma pneumoniae Infection

Infect Immun. 2020 Aug 19;88(9):e00099-20. doi: 10.1128/IAI.00099-20. Print 2020 Aug 19.

Abstract

Human surfactant protein-A2 (hSP-A2) is a component of pulmonary surfactant that plays an important role in the lung's immune system by interacting with viruses, bacteria, and fungi to facilitate pathogen clearance and by downregulating inflammatory responses after an allergic challenge. Genetic variation in SP-A2 at position Gln223Lys is present in up to ∼30% of the population and has been associated with several lung diseases, such as asthma, pulmonary fibrosis, and lung cancer (M. M. Pettigrew, J. F. Gent, Y. Zhu, E. W. Triche, et al., BMC Med Genet 8:15, 2007, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-8-15; Y. Wang, P. J. Kuan, C. Zing, J. T. Cronkhite, et al., Am J Hum Genet 84:52-59, 2009, https://www.cell.com/ajhg/fulltext/S0002-9297(08)00595-8). Previous work performed by our group showed differences in levels of SP-A binding to non-live mycoplasma membrane fractions that were dependent on the presence of a lysine (K) or a glutamine (Q) at amino acid position 223 in the carbohydrate region of SP-A2. On the basis of these differences, we have derived 20-amino-acid peptides flanking this region of interest in order to test the ability of each to regulate various immune responses to live Mycoplasma pneumoniae in SP-A knockout mice and RAW 264.7 cells. In both models, the 20-mer containing 223Q significantly decreased both tumor necrosis factor alpha (TNF-α) mRNA levels and protein levels in comparison to the 20-mer containing 223K during M. pneumoniae infection. While neither of the 20-mer peptides (223Q and 223K) had an effect on p38 phosphorylation during M. pneumoniae infection, the 223Q-20mer peptide significantly reduced NF-κB p65 phosphorylation in both models. Taken together, our data suggest that small peptides derived from the lectin domain of SP-A2 that contain the major allelic variant (223Q) maintain activity in reducing TNF-α induction during M. pneumoniae infection.

Keywords: Mycoplasma pneumoniae; NF-κB; SP-A2; tumor necrosis factor alpha.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / immunology
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / pharmacology*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Host Microbial Interactions / genetics
  • Host Microbial Interactions / immunology*
  • Humans
  • Lung / drug effects
  • Lung / immunology
  • Lung / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycoplasma pneumoniae / drug effects
  • Mycoplasma pneumoniae / immunology*
  • Mycoplasma pneumoniae / pathogenicity
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / microbiology
  • Peptides / chemical synthesis
  • Peptides / pharmacology*
  • Pneumonia, Mycoplasma / drug therapy*
  • Pneumonia, Mycoplasma / genetics
  • Pneumonia, Mycoplasma / immunology
  • Pneumonia, Mycoplasma / microbiology
  • Protein Domains
  • Pulmonary Surfactant-Associated Protein A / chemistry
  • Pulmonary Surfactant-Associated Protein A / deficiency
  • Pulmonary Surfactant-Associated Protein A / genetics
  • Pulmonary Surfactant-Associated Protein A / immunology*
  • RAW 264.7 Cells
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Signal Transduction
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / immunology

Substances

  • Adhesins, Bacterial
  • Anti-Inflammatory Agents
  • Peptides
  • Pulmonary Surfactant-Associated Protein A
  • RNA, Messenger
  • Rela protein, mouse
  • SFTPA2 protein, human
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • adhesin, Mycoplasma pneumoniae
  • p38 Mitogen-Activated Protein Kinases