Chapter 17
Complement Resistance Assays
Lourdes Isaac and Angela Silva Barbosa
Abstract
Like many other pathogens of medical importance, pathogenic Leptospira employ diverse strategies to
circumvent Complement System activation. Under physiological conditions, this central humoral arm of
innate immunity is tightly controlled by negative Complement regulatory proteins. However, upon
infection, pathogenic microorganisms interfere with normal Complement host defense mechanisms by
recruiting or mimicking Complement regulators and by secreting endogenous proteases or acquiring host’s
proteases that inactivate key Complement components. In this chapter, we describe in detail some of the
most frequently used assays to evaluate Leptospira Complement resistance.
Key words Complement, Leptospira, Complement regulators, Serum susceptibility, Cleavage of
Complement proteins, Proteases
1 Introduction
The Complement System is important for the innate and acquired
immune responses against several pathogens. Once activated, this
System generates several important biological functions that may
help to control infection and bacteria dissemination such as
(a) generation of opsonins (fragments C3b, iC3b, and C3d)
which contribute to enhance microorganism internalization and
killing by macrophages and other phagocytic cells; (b) formation
of a pore on the microorganism surface called membrane attack
complex (C5b6789 n ) which may lead to pathogen lysis;
(c) production of chemoattractant factors (fragments C3a and
C5a) attracting more inflammatory cells toward the infected tissue;
and (d) stimulating the production of specific antibodies against
pathogens (fragment C3d/C3dg and receptor CR2) (reviewed in
[1]).
To avoid excessive activation of this System and consequently
host cell damage, several regulatory proteins control the Alternative
Pathway [e.g., Factor H (FH), FH-like (FHL)-1, Factor I] as well
as the Classical and the Lectin Pathways [e.g., C1 inhibitor,
Nobuo Koizumi and Mathieu Picardeau (eds.), Leptospira spp.: Methods and Protocols, Methods in Molecular Biology, vol. 2134,
https://doi.org/10.1007/978-1-0716-0459-5_17, © Springer Science+Business Media, LLC, part of Springer Nature 2020
187
Complement Resistance Assays
Lourdes Isaac and Angela Silva Barbosa
Abstract
Like many other pathogens of medical importance, pathogenic Leptospira employ diverse strategies to
circumvent Complement System activation. Under physiological conditions, this central humoral arm of
innate immunity is tightly controlled by negative Complement regulatory proteins. However, upon
infection, pathogenic microorganisms interfere with normal Complement host defense mechanisms by
recruiting or mimicking Complement regulators and by secreting endogenous proteases or acquiring host’s
proteases that inactivate key Complement components. In this chapter, we describe in detail some of the
most frequently used assays to evaluate Leptospira Complement resistance.
Key words Complement, Leptospira, Complement regulators, Serum susceptibility, Cleavage of
Complement proteins, Proteases
1 Introduction
The Complement System is important for the innate and acquired
immune responses against several pathogens. Once activated, this
System generates several important biological functions that may
help to control infection and bacteria dissemination such as
(a) generation of opsonins (fragments C3b, iC3b, and C3d)
which contribute to enhance microorganism internalization and
killing by macrophages and other phagocytic cells; (b) formation
of a pore on the microorganism surface called membrane attack
complex (C5b6789 n ) which may lead to pathogen lysis;
(c) production of chemoattractant factors (fragments C3a and
C5a) attracting more inflammatory cells toward the infected tissue;
and (d) stimulating the production of specific antibodies against
pathogens (fragment C3d/C3dg and receptor CR2) (reviewed in
[1]).
To avoid excessive activation of this System and consequently
host cell damage, several regulatory proteins control the Alternative
Pathway [e.g., Factor H (FH), FH-like (FHL)-1, Factor I] as well
as the Classical and the Lectin Pathways [e.g., C1 inhibitor,
Nobuo Koizumi and Mathieu Picardeau (eds.), Leptospira spp.: Methods and Protocols, Methods in Molecular Biology, vol. 2134,
https://doi.org/10.1007/978-1-0716-0459-5_17, © Springer Science+Business Media, LLC, part of Springer Nature 2020
187