Immune Evasion of Moraxella catarrhalis Involves Ubiquitous Surface Protein A-Dependent C3d Binding.

Hallström, TeresiaLund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups (author)

The complement system plays an important role in eliminating invading pathogens. Activation of complement results in C3b deposition (opsonization), phagocytosis, anaphylatoxin (C3a, C5a) release, and consequently cell lysis. Moraxella catarrhalis is a human respiratory pathogen commonly found in children with otitis media and in adults with chronic obstructive pulmonary disease. The species has evolved multiple complement evasion strategies, which among others involves the ubiquitous surface protein (Usp) family consisting of UspA1, A2, and A2 hybrid. In the present study, we found that the ability of M. catarrhalis to bind C3 correlated with UspA expression and that C3 binding contributed to serum resistance in a large number of clinical isolates. Recombinantly expressed UspA1 and A2 inhibit both the alternative and classical pathways, C3b deposition, and C3a generation when bound to the C3 molecule. We also revealed that the M. catarrhalis UspA-binding domain on C3b was located to C3d and that the major bacterial C3d-binding domains were within UspA1(299-452) and UspA2(165-318). The interaction with C3 was not species specific since UspA-expressing M. catarrhalis also bound mouse C3 that resulted in inhibition of the alternative pathway of mouse complement. Taken together, the binding of C3 to UspAs is an efficient strategy of Moraxella to block the activation of complement and to inhibit C3a-mediated inflammation.

Nordström, TheréseLund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine,Clinical Microbiology, Malmö,Lund University Research Groups(Swepub:lu)mikr-tno (author)
Tan, Thuan Tong (author)
Manolov, Taras (author)
Lambris, John D (author)
Isenman, David E (author)
Zipfel, Peter F (author)
Blom, AnnaLund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-abl (author)
Riesbeck, KristianLund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups(Swepub:lu)mikr-kri (author)
Klinisk mikrobiologi, MalmöForskargrupper vid Lunds universitet (creator_code:org_t)

In:Journal of immunology: The American Association of Immunologists186, s. 3120-31291550-66060022-1767

By the author/editor: Hallström, Teres ...; Nordström, Theré ...; Tan, Thuan Tong; Manolov, Taras; Lambris, John D; Isenman, David E; show more...; Zipfel, Peter F; Blom, Anna; Riesbeck, Kristi ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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